04122023Department of Pharmaceutics 1

Seminar on helliphellip

ISO series guide of pharmaceutical manufacturing facilities productivity

By

Mr Kailash Vilegave

Assit prof

Shivajirao S Jondhle college of pharmacy Asangaon 421601

04122023Department of Pharmaceutics 2

Contents

Introduction History ISO 9000 series ISO14000 series Guide to Pharmaceutical

Manufacturing Facilities Productivity References

04122023Department of Pharmaceutics 3

IntroductionWhat are ISO 9000 Standards

ISO 9000 Standards Define the required elements of an effective

quality management system Can be applied to any company Adopted by the United States as the

ANSIASQC Q90 series

154 COUNTRIES

Bureau of Standards Jamaica

STANDARD BODIES

04122023Department of Pharmaceutics 4

bull ISO WAS FORMED FEBRUARY 23 1947 IN GENEVA

bull FIRST FAMILY OF QUALITY STANDARD RELEASED 1987ndash To eliminate country to country differencesndash To eliminate terminology confusionndash To increase quality awareness

bull FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996

Background Who Created Standards

04122023Department of Pharmaceutics 5

How did ISO get started

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

04122023Department of Pharmaceutics 6

ISO 9000 Consists of 5 Documents

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test

ISO 9004 Quality Management and Quality System Elements - Guidelines

ISO 9004 Quality Management and Quality System Elements - Guidelines

04122023Department of Pharmaceutics 7

ISO 9000 Family of Standards

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management

04122023Department of Pharmaceutics 8

What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality

management and quality assurancebull ISO 14000 series provides a similar framework for

environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies

and languages

bull AS 9100 the Aerospace Basic Quality System Standard

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 2

Contents

Introduction History ISO 9000 series ISO14000 series Guide to Pharmaceutical

Manufacturing Facilities Productivity References

04122023Department of Pharmaceutics 3

IntroductionWhat are ISO 9000 Standards

ISO 9000 Standards Define the required elements of an effective

quality management system Can be applied to any company Adopted by the United States as the

ANSIASQC Q90 series

154 COUNTRIES

Bureau of Standards Jamaica

STANDARD BODIES

04122023Department of Pharmaceutics 4

bull ISO WAS FORMED FEBRUARY 23 1947 IN GENEVA

bull FIRST FAMILY OF QUALITY STANDARD RELEASED 1987ndash To eliminate country to country differencesndash To eliminate terminology confusionndash To increase quality awareness

bull FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996

Background Who Created Standards

04122023Department of Pharmaceutics 5

How did ISO get started

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

04122023Department of Pharmaceutics 6

ISO 9000 Consists of 5 Documents

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test

ISO 9004 Quality Management and Quality System Elements - Guidelines

ISO 9004 Quality Management and Quality System Elements - Guidelines

04122023Department of Pharmaceutics 7

ISO 9000 Family of Standards

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management

04122023Department of Pharmaceutics 8

What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality

management and quality assurancebull ISO 14000 series provides a similar framework for

environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies

and languages

bull AS 9100 the Aerospace Basic Quality System Standard

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 3

IntroductionWhat are ISO 9000 Standards

ISO 9000 Standards Define the required elements of an effective

quality management system Can be applied to any company Adopted by the United States as the

ANSIASQC Q90 series

154 COUNTRIES

Bureau of Standards Jamaica

STANDARD BODIES

04122023Department of Pharmaceutics 4

bull ISO WAS FORMED FEBRUARY 23 1947 IN GENEVA

bull FIRST FAMILY OF QUALITY STANDARD RELEASED 1987ndash To eliminate country to country differencesndash To eliminate terminology confusionndash To increase quality awareness

bull FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996

Background Who Created Standards

04122023Department of Pharmaceutics 5

How did ISO get started

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

04122023Department of Pharmaceutics 6

ISO 9000 Consists of 5 Documents

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test

ISO 9004 Quality Management and Quality System Elements - Guidelines

ISO 9004 Quality Management and Quality System Elements - Guidelines

04122023Department of Pharmaceutics 7

ISO 9000 Family of Standards

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management

04122023Department of Pharmaceutics 8

What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality

management and quality assurancebull ISO 14000 series provides a similar framework for

environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies

and languages

bull AS 9100 the Aerospace Basic Quality System Standard

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 4

bull ISO WAS FORMED FEBRUARY 23 1947 IN GENEVA

bull FIRST FAMILY OF QUALITY STANDARD RELEASED 1987ndash To eliminate country to country differencesndash To eliminate terminology confusionndash To increase quality awareness

bull FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996

Background Who Created Standards

04122023Department of Pharmaceutics 5

How did ISO get started

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

04122023Department of Pharmaceutics 6

ISO 9000 Consists of 5 Documents

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test

ISO 9004 Quality Management and Quality System Elements - Guidelines

ISO 9004 Quality Management and Quality System Elements - Guidelines

04122023Department of Pharmaceutics 7

ISO 9000 Family of Standards

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management

04122023Department of Pharmaceutics 8

What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality

management and quality assurancebull ISO 14000 series provides a similar framework for

environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies

and languages

bull AS 9100 the Aerospace Basic Quality System Standard

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 5

How did ISO get started

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1906 - International Electro-technical Commission

1926 - International Federation of the National Standardizing Associations (ISA)

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the

international coordination and unification of industrial standards

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

1947 - ISO began to officially function

1951 - The first ISO standard was published

Standard reference temperature for industrial length measurement

04122023Department of Pharmaceutics 6

ISO 9000 Consists of 5 Documents

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test

ISO 9004 Quality Management and Quality System Elements - Guidelines

ISO 9004 Quality Management and Quality System Elements - Guidelines

04122023Department of Pharmaceutics 7

ISO 9000 Family of Standards

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management

04122023Department of Pharmaceutics 8

What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality

management and quality assurancebull ISO 14000 series provides a similar framework for

environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies

and languages

bull AS 9100 the Aerospace Basic Quality System Standard

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 6

ISO 9000 Consists of 5 Documents

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9000 Quality Management and Quality Assurance Standards

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9002 Quality Systems - QA Model for Production and Installation (no design)

ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test

ISO 9004 Quality Management and Quality System Elements - Guidelines

ISO 9004 Quality Management and Quality System Elements - Guidelines

04122023Department of Pharmaceutics 7

ISO 9000 Family of Standards

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management

04122023Department of Pharmaceutics 8

What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality

management and quality assurancebull ISO 14000 series provides a similar framework for

environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies

and languages

bull AS 9100 the Aerospace Basic Quality System Standard

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 7

ISO 9000 Family of Standards

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software

ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-2 Guidelines for services

ISO 9004-3 Guidelines for processed material

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

ISO 9004-4 Guidelines for quality improvement

ISO 9004-5 Guidelines for quality plans

bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management

04122023Department of Pharmaceutics 8

What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality

management and quality assurancebull ISO 14000 series provides a similar framework for

environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies

and languages

bull AS 9100 the Aerospace Basic Quality System Standard

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 8

What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality

management and quality assurancebull ISO 14000 series provides a similar framework for

environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies

and languages

bull AS 9100 the Aerospace Basic Quality System Standard

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 9

ISO 90001987 seriesISO 90001987 series

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

International Organisation for Standards (ISO) adopted

a series of quality standards ISO 90001987

based on BS5750

strongly influenced by the US Department of Defence

Military Standards (MILspecs)

initial version was focused on quality control using

retroactive checkingand corrective actions

ISO 90001994 seriesISO 90001994 series

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

ISO 9000 was revised in 1994

greater emphasis on quality assurance via preventive

actions

required evidence of compliance with

documented procedures

tended to create a significant volume of associated procedure

(do it as you document it) manuals and bureaucracy

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 10

QS-9000QS-9000

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

Ford Chrysler General Motors and other automotivetruck

manufacturers identified deficiencies in ISO90001994

undertook a re-interpretation and

extension to develop QS-9000

additionally addressed continuous improvement manufacturing capability

and production part approval processes

ISO90002000 seriesISO90002000 series

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

2nd revision of Quality Management System

Requirement Standard from International Organization for

Standards

moved towardsprocess performance metrics

reduced the need fordocumented procedures

where clear evidence exists that the process is working

well

Replacement for previous ISO 9001 9002 and 9003

standards of 1994

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 11

ISO90002000 series standards provide criteria

for companies to certify their quality

management recertification is

required every three years

achieve registration by third-party auditor

the system verifies practice and

processes provides objective 3rd

party validation enables benchmarking

TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version

Future Version 2008

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 12

New ISO 9001

QMSResource

management

Measurement analysis amp

improvements

Product Realization

Management

Responsibility

Continual Improvement cycle

General requirements

General requirements

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 13

ISO 9001 Model

CU

ST

OM

ER

SC

US

TO

ME

RS

Quality Management

System

5ManagementResponsibility

7 ProductRealization

6 ResourceManagement

8 MeasurementAnalysis and Improvement

Requirements

Satisfaction

Continual Improvement ofthe Quality Management System

ConsumptionProduct

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 14

Principle Of New Standards

Based on eight quality

management principles

Based on eight quality

management principles

LeadershipLeadership

Process approach

Process approach

Involvement of people

Involvement of people

System approach

to Manageme

nt

System approach

to Manageme

nt

Continual improveme

nt

Continual improveme

nt

Factual approach

to decision making

Factual approach

to decision making

Mutual beneficial supplier

relationship

Mutual beneficial supplier

relationship

Customer focus

Customer focus

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 15

Principles of new standard

Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations

Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve

organizationrsquos objectives

Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit

Process approachDesired results are achieved more efficiently when activities and

resources are managed as process

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 16

Principles of new standard

System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency

Continual improvementsContinual improvement of the organizationrsquos overall performance

should be a permanent objective of the organization

Factual approach to decision makingEffective decisions are based on the analysis of data and information

Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to

create value

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 17

Expectations of the new Standard

Avoid the application of systems that are separate from the organizationrsquos business process

Avoid the application of systems that are separate from the organizationrsquos business process

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business

Enable Continual improvements of the system for enhanced customer satisfaction

Enable Continual improvements of the system for enhanced customer satisfaction

Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 18

Important changes

+ Why it is to be doneWhat to do When Whom amp How to do

Involvement of people

Continual improvements should be achieved

Maintain the system requirements

Improvements

+ Statutory amp regulatory requirements

Requirements specified by customer organization

Product requirements

Value adding processes20 quality elementsApproach

Customer satisfactionProductsMain focus

New VersionPrevious versionCriteria

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 19

Process approach

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Process definition Set of interrelated or interacting activities which transforms

inputs into outputs

Ensure continual

improvements

Ensure continual

improvements

Identify the

processes

Identify the

processes

Do it for all value adding processes Do it for all value adding processes

Establish measuring criteria

Establish measuring criteria

Identify the Interactions to other processes

Identify the Interactions to other processes

Identify the Inputs amp outputs

Identify the Inputs amp outputs

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 20

Process approach ndash Continual improvements of Process

PDCA Cycle

Processes in terms

Of Added Value

DO

Continual improvements

of Processes based on

objective measurements

ACTION

Measure results of process

Performance and effectiveness

- Objective Measurements

CHECK

Understandings amp

meeting requirements

PLAN

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 21

System Requirements Structure of the Standard

Provision of resources

Human resources

Infrastructures

Work environment

6 ISO9000 structure II Resource Management

General requirements

Documentation Requirements

Planning

Customer related processes

Design amp development

Purchasing

Production amp service provision

Management Commitment

Customer focus

Quality policy

Planning

Responsibility authority amp communication

Management Reviews

5 ISO9000 structure I Management Responsibility

8 ISO9000 structure IV Measurement Analysis ampimprovement

4 Quality Management System

7 ISO9000 structure III Product Realization

General

Monitoring amp measurement

Control of NCP

Analysis of data

Improvements

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 22

4 - Quality management system

41 General

requirements

Identification

of processes

required

Criteria and

methods to ensure

Operation amp control

Availability of

information amp

resources for

operation amp control

Monitoring and

Measuring of

processes

Continual

improvements

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 23

4 - Quality management system

Quality Policy

Quality Objectives

Quality Manual

Procedures required by the Standard

Procedures required for planning operation

amp control of Organization activities

Records

42 Document requirements

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 24

5 - Management Responsibility

56 Responsibility authority amp communicate

54 Planning

51 Management commitment

52 Customer focus

57 Management Review

53 Quality policy

Quality objectives

QMS planning

General

Review inputs

Review outputsInternal

communication

Management representative

Responsibility amp authority

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 25

5 - Management Responsibility

Development implementation and continually improvement of QMS

Development implementation and continually improvement of QMS

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

bull Appointment of Management Representativebull Conducting Management

Reviews

bull Providing required resources

Establishment ofbull Quality Policybull Quality Objectives

Establishment ofbull Quality Policybull Quality Objectives

Identification of Customer requirementsIdentification of Customer requirements

Top Managementrsquos commitment

Top Managementrsquos commitment

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 26

6 - Resource Management

64

Work Environment

63 Infrastructures

62

Human Resources

General

Competence awareness amp training

61

Provision of resources

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 27

6 - Resource Management

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements

Human ResourcesHuman Resources

InfrastructuresInfrastructures needed to achieve product conformity

InfrastructuresInfrastructures needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Work environmentWork environment needed to achieve product conformity

Resource Managemen

t

Resource Managemen

t

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 28

6 - Human Resources

Competent on the basis of appropriate education skill and experience

Competent on the basis of appropriate education skill and experience

Define competencies for people performing work affecting product quality

Define competencies for people performing work affecting product quality

Provide training or actionsProvide training or actions

Evaluate effectiveness of the training actions

Evaluate effectiveness of the training actions

Employees should aware importance of the activity being performed

Employees should aware importance of the activity being performed

62 Human

Resources

62 Human

Resources

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 29

7 - Product Realization

76

Control of monitoring measuring devices

Control

Preservation of product

Validation of processes

Identification amp traceability

Customer property

75

Production amp service provision

Verification of purchased products

Purchasing process

Purchasing information

74

Purchasing

Design planning

Design inputs

Design outputs

Design review

Design Changes

Design validation

Design verification

73

Design and development

71

Planning of product realization

Identification of customer requirement

Review of customer requirement

Customer communication

72

Customer related processes

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 30

7 - Product Realization

Quality objectives of ProductsQuality objectives of Products

Processes procedures to realize product

Processes procedures to realize product

Verification validation monitoring inspection and testing of product

Verification validation monitoring inspection and testing of product

Record to demonstrate conformanceRecord to demonstrate conformance

71

Planning of Product realization

71

Planning of Product realization

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 31

7 - Product Realization

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Effective communication with customer in relation to

bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements

Identification of Customer Market requirements

bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72

Customer related processes ndash (Sales)

72

Customer related processes ndash (Sales)

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 32

7 - Product Realization

Design inputs and outputsDesign inputs and outputs

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned

Planningbull Effective amp efficientbull Expectations of interested parties

Planningbull Effective amp efficientbull Expectations of interested parties

73

Design and Development ndash

(Product)

73

Design and Development ndash

(Product)

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 33

7 - Product Realization

Supplier evaluationSupplier evaluation

Verification of purchased product ndash Inspection and testing

Verification of purchased product ndash Inspection and testing

Degree of control depends on effects of subsequent processes and effect on final product

Degree of control depends on effects of subsequent processes and effect on final product

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

74

Purchasing

Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 34

7 - Product Realization

Product characteristics

Product characteristics

Procedures and work instructionsProcedures and work instructions

Suitable equipments to manufacture Monitoring and inspection amp testing

Suitable equipments to manufacture Monitoring and inspection amp testing

Product release delivery and post delivery

Product release delivery and post delivery

Process validationProcess validation

Identification and traceability Identification and traceability

Customers property

Material supplied by customers ndash eg 3rd party blending

Customers property

Material supplied by customers ndash eg 3rd party blending

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

75

Production and service provision

Manufacturing service provision under controlled condition to ensure conformity of product

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 35

8 - Measurement analysis and improvement

82

Monitoring amp measurements

84

Analysis of data

85

Improvement

83 Control of non conforming product

Measurement of product

Internal audits

Customer satisfaction

Measurement of processes

Corrective action

Preventive action

Continual improvements

81

General

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 36

8 - Measurement analysis and improvement

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and

ISO9001bull Monitoring and measurements of processes ndash to determine

demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to

product requirements

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

83 - Control of NCPbull To assure that NCP products are identified and controlled to

prevent unintended use delivery

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 37

8 - Measurement analysis and improvement

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system

Analysis shall provide information related to

bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 38

8 - Measurement analysis and improvement

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

85 - ImprovementsContinual Improvements

bull QMS needed to be continually improved

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action

implementation of action review of action and maintenance

of relevant records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

Preventive actionbull Actions against potential non conformities to avoid their

occurrencebull Includes identification of potential non conformities cause

need for action implementation of action review of action

and maintenance of records

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 39

Criteria for measurements

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested

parties

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost

Self assessment

Self assessment

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

ndash Satisfaction surveys for customers and other interested parties

bull Feedback on productsbull Customer amp market requirements

System performanc

e

System performanc

e

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 40

Criteria for measurements

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Inspection and testing of incoming in process and final

productndash Product verificationndash Product validation

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ndash Process capability process validation

ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction

ProductsProducts

Processes

Processes

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 41

What is ISO 14000

Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management

Minimize harmful effects on the environmentMinimize harmful effects on the environment

Continual Improvement of environmental performanceContinual Improvement of environmental performance

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14000

EMS- General Guidelines on Principles Systems and Supporting Techniques

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

ISO 14001

EMS- Specification with Guidance for Use requires a

substantial commitment of time and resources

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 42

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14004

EMS - General Guidelines on Systems Principles and

Supporting Techniques

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14010

EA- General Principles of Environmental Auditing

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14011

EA- Auditing of Environmental Management

Systems

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14012

EA- Qualification Criteria for Environmental Auditors

ISO 14013

Management of Environmental Audit

Programs

ISO 14013

Management of Environmental Audit

Programs

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14014

Initial Reviews

ISO 14015

Environmental Site Assessments

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14020

EL- Basic Principles of Environmental Labeling

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

ISO 14021

EL- Self Declaration- Environmental Claims- Terms

and Definitions

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 43

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14022 EL- Symbols

ISO 14023

EL- Testing and Verification Methodologies

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14024

EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)

ISO 14031

Environmental Performance Evaluation

ISO 14031

Environmental Performance Evaluation

ISO 14040

LCA- General Principles and Practices

ISO 14040

LCA- General Principles and Practices

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14041

LCA- Goal and DefinitionScope and

Inventory Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14042

LCA- Impact Assessment ISO 14043

LCA- Improvement Assessment

ISO 14050

Terms and Definitions

ISO 14050

Terms and Definitions

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

ISO 14060

Guide for the Inclusion of Environmental Aspects in

Product Standards

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 44

Guides To Pharmaceutical Manufacturing Facilities amp Productivity

Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 45

Need of guidelines in pharmaceuticals

facilities amp productivity Detailed guidelines of a system so that

the findings reflect the state of control in that system for every product (profile) class

If one of the six systems is out of control the firm is considered out of control

A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 46

Quality System

Quality must be built into the process

Quality must be built into the process

Quality is not tested into the productQuality is not tested into the product

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Assurance of Quality comes from- Design of robust process based on

thorough knowledge of that process and the sources of variability

Effective Quality System in place Effective Quality System in place

Quality System

Quality System

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 47

Role of Management in QS

Management is responsible for

Organizational structure All Processes All Procedures Facilities amp Resources

In short everything to insure product quality customer satisfaction and continuous improvement

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 48

Quality System Responsibilities

Assures overall compliance with cGMPs

Review and approval duties for

1)Product Quality Reviews (at least annually)

2)Complaint reviews

3)Discrepancy failure investigations

4)Change Control

5)CAPA (Corrective And Preventive Action)

6) Reprocess Rework

7) Validation Revalidation

8) Rejects

9) Stability Failures Out of trend data

10) Quarantine products

11) Documented GMP amp Job Related Training

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 49

Laboratory Control System (I)

Adequately staffed laboratories (supervisory and bench personnel)

Adequately staffed laboratories (supervisory and bench personnel)

Written specifications for raw materials intermediates APIs labels amp packaging

Written specifications for raw materials intermediates APIs labels amp packaging

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data

Method validation revalidationMethod validation revalidation

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

Laboratory Control System

Adequate lab facilities under the Quality Unit which is independent from Production

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 50

Laboratory Control System (II)

Reference Standards (primary secondary)Reference Standards (primary secondary)

Laboratory controls followed and documented

Laboratory controls followed and documented

Calibration written procedures schedule documentation

Calibration written procedures schedule documentation

Equipment QualificationEquipment Qualification

Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 51

Laboratory Control System (III)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented

ldquooosrdquo review included in Product Quality Reviews

ldquooosrdquo review included in Product Quality Reviews

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Description of samplesIdentification of method used

Raw data for sample standard preparation reagents

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 52

Laboratory Control System (IV)

Complete record of all data from testingRecord of all calculations

Complete record of all data from testingRecord of all calculations

Statement of the test results how compare with established acceptance criteria

Statement of the test results how compare with established acceptance criteria

Signature of the person who performed each test dates tests performed

Signature of the person who performed each test dates tests performed

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards

Laboratory Control System

Laboratory Control System

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 53

Production System (I)

Production System (I)

Master production and control

records

Master production and control

records

Change control

procedure

Change control

procedure

Batch production and control

records

Batch production and control

records

Contemporaneous accurate and complete

batch production documentation

Contemporaneous accurate and complete

batch production documentation

Implementation and documentation of in-process controls tests and examinations

Implementation and documentation of in-process controls tests and examinations

Training (documente

d job-related)

Training (documente

d job-related)

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 54

Production system (II)

Identification of equipment with contents

stage of manufacturing status

Equipment cleaning records

Established time limits for completion of

production steps stages

Deviations investigated and documented

contemporaneously with investigation

Adequate written procedures amp practice

for charge-in of materials

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 55

Production system (III)

Justification and consistency of in-process specifications and final product specifications

Data information documented and available to Quality Unit for review (trending investigations etc)

Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 56

Facilities amp Equipment System

Location design construction appropriate to facilitate cleaning maintenance operations

Location design construction appropriate to facilitate cleaning maintenance operations

Layout and air handling designed and constructed to prevent cross-

contamination

Layout and air handling designed and constructed to prevent cross-

contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Flow of materials amp personnel designed to prevent mix-ups or contamination

Defined areas or other control systems to prevent mix-ups or contamination includes as

Defined areas or other control systems to prevent mix-ups or contamination includes as

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 57

Facilities amp Equipment System

Incoming materials (id quarantine)

Incoming materials (id quarantine) Sampling area (prevent

contamination)

Sampling area (prevent contamination)

Quarantine (intermediates APIs)Quarantine (intermediates APIs)

Released materialsReleased materials

RejectionRejection

b) EQUIPMENTSb) EQUIPMENTS

Appropriate design size location non-reactive product contact surfaces

Appropriate design size location non-reactive product contact surfaces

Facilities amp Equipment System

Facilities amp Equipment System

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 58

Facilities amp Equipment System

Identification clearly marked

Identification clearly marked CalibrationCalibration

Preventive Maintenance schedule and procedures

Preventive Maintenance schedule and procedures

Cleaning procedures and validationCleaning procedures and validation

Records of use cleaning maintenance

Records of use cleaning maintenance

Closed or contained equipment - Inspection prior to use

Closed or contained equipment - Inspection prior to use

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Separate facilities or containment where needed (penicillins highly potent compounds etc)

Facilities amp Equipment System b) EQUIPMENTS

Facilities amp Equipment System b) EQUIPMENTS

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 59

Utilities

Qualified and appropriately monitored drawings should be available

Qualified and appropriately monitored drawings should be available

Designed and constructed to prevent contamination or cross-contamination

Designed and constructed to prevent contamination or cross-contamination

Recirculated air to production (same concern)

Recirculated air to production (same concern)

Permanently installed pipe work should be appropriately identified

Permanently installed pipe work should be appropriately identified

Drains of adequate size with air breakDrains of adequate size with air break

UtilitiesUtilities

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 60

Water

Process water at minimum meeting WHO guidelines for potable water

Process water at minimum meeting WHO guidelines for potable water

Justify quality of water used to achieve stated API quality and

establish specifications

Justify quality of water used to achieve stated API quality and

establish specifications

Water treatment facilities validationWater treatment facilities validation

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts

objectionable organisms and endotoxins

WaterWater

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 61

Materials System

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

Written procedures for receipt identification quarantine storage handling sampling testing and

approval or rejection of materials

System to evaluate suppliers (critical materials)Purchased against agreed specification

System to evaluate suppliers (critical materials)Purchased against agreed specification

Change control process for changing suppliers

Change control process for changing suppliers

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Upon receipt check for correct labeling seals

Before co-mingling bulk material idtest

Assurances obtained from non-dedicated tankers

Assurances obtained from non-dedicated tankers

Materials System

Materials System

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 62

Materials System

Identification on large storage containers and associated manifolds filling and discharge lines

Identification on large storage containers and associated manifolds filling and discharge lines

Code given to received batches status identityCode given to received batches status identity

At minimum a specific identity test on incoming batches

At minimum a specific identity test on incoming batches

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Supplier evaluation should include three fully tested batches one fully tested

batchyear

Written sampling plan with justificationPrevent contamination of sampled containers

Written sampling plan with justificationPrevent contamination of sampled containers

Materials System

Materials System

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 63

Materials SystemStored in manner to prevent degradation

contamination no adverse effect on quality

Stored in manner to prevent degradation contamination no adverse effect on quality

Drums bags boxes off the floorDrums bags boxes off the floor

First in first outFirst in first out

Rejected materials identified and controlled under a quarantine system

Rejected materials identified and controlled under a quarantine system

Established re-test re-evaluation periodsEstablished re-test re-evaluation periods

Materials System

Materials System

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 64

Packaging amp Labeling System

PampL should conform to specifications

Records maintained for each shipment

(showing receipt examination amp result)

Containers protective clean not alter product quality if re-used cleaned amp labeling defaced

Access to label storage area limited

Written procedures for reconciliation

- investigation if discrepancy

Written procedures for receipt identification quarantine sampling examination andor testing PampL

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 65

Packaging amp Labeling System

Obsolete labels destroyed

Printing devices controlled to insure accuracy of label (against batch record)

Print labels checked against master and a copy placed into the batch record

Documented procedures to assure correct

packaging materials labels used

Operations designed to prevent mix-ups

All excess labels with batch destroyed

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 66

Packaging amp Labeling System

Shipped API Name address manufacturer special

transport conditions expiry retest date

Documented clearance before operations

Packaged labeled intermediates or APIs examined as part of packaging (documented)

Seal employed to assure package integrity

Labels API name batch storage conditions

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 67

Benefits Certification demonstrates the

recognition of quality throughout organization

Decrease in wasted time materials and efforts

Inculcating values of excellence and best practices

Establish leadership role within organization

Increased recognition by international partners

Ability to maintain standards of quality and excellence

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 68

References

Lachman L Lieberman A Kanig JL The

Theory Of Industrial Pharmacy 2nd edi

Varghese Publication House Bombay-14

Gilbert s Banker Christoher T Rhodes

Modern Pharmaceutics 3rd edi New York

Sharma PP How To Practice GMPs 2nd edi

Vandana Publication Agra

wwwgooglecom

wwwwikipediacom

wwwkwalitegcozaiso9000com

wwwfdacom

04122023Department of Pharmaceutics 69

• Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
• Contents
• Introduction What are ISO 9000 Standards
• Slide 4
• How did ISO get started
• ISO 9000 Consists of 5 Documents
• Slide 7
• Slide 8
• Slide 9
• Slide 10
• ISO90002000 series
• New ISO 9001
• ISO 9001 Model
• Principle Of New Standards
• Principles of new standard
• Principles of new standard (2)
• Expectations of the new Standard
• Important changes
• Process approach
• Process approach ndash Continual improvements of Process
• System Requirements Structure of the Standard
• 4 - Quality management system
• 4 - Quality management system (2)
• 5 - Management Responsibility
• 5 - Management Responsibility
• 6 - Resource Management
• 6 - Resource Management (2)
• 6 - Human Resources
• 7 - Product Realization
• 7 - Product Realization (2)
• 7 - Product Realization (3)
• 7 - Product Realization (4)
• 7 - Product Realization (5)
• 7 - Product Realization (6)
• 8 - Measurement analysis and improvement
• 8 - Measurement analysis and improvement
• 8 - Measurement analysis and improvement (2)
• 8 - Measurement analysis and improvement (2)
• Criteria for measurements
• Criteria for measurements (2)
• What is ISO 14000
• Slide 42
• Slide 43
• Guides To Pharmaceutical Manufacturing Facilities amp Productivit
• Need of guidelines in pharmaceuticals facilities amp productivity
• Slide 46
• Role of Management in QS
• Quality System Responsibilities
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Slide 53
• Production system (II)
• Production system (III)
• Slide 56
• Slide 57
• Slide 58
• Slide 59
• Slide 60
• Slide 61
• Slide 62
• Slide 63
• Slide 64
• Slide 65
• Slide 66
• Benefits
• References
• Slide 69