A Seminar On Quality Audit

M.Pharm (Quality assurance)

Prepared by :-

Paras Shah

Guided By :-

Mr. Dhaval Rathod

Contents

Definition Objectives Difference between Quality audit and Periodic

evaluation Self inspection Types of Quality Audit Role OF GMP Audit in QA and QC programmes Elements of a Systemic Audit program

Quality Audit

Quality audit is defined as a systematic and independent examination to determine whether activities and related results comply with planned arrangements and whether these arrangements are implemented effectively and are suitable to achieve objectives

1.Quality Audit

Quality audit means a systematic examination of a quality system.

Quality audits are typically performed at defined intervals

Any failure in their proper implementation may be published publicly and may lead to a revocation of quality certification

2.Objectives Of Quality Audit Pharmaceutical manufacturers commonly use

audits as an effective mechanism to verify compliance with GMP regulation (GMP).GMP audits with two important goals

Audis are intended to verify that manufacturing and Control systems are operating under a state of control.

Audits permit timely correction of potential problems.

Audits can be used to establish a high degree of confidence to remain under an adequate level of control by managements

3.Difference between Audit and Periodic Evaluation

Quality audit 

Periodic Evaluation

Quality audit is Periodic, independent, and documented examination and verification of activities, records, processes, and other elements of a quality system to determine their conformity with the requirements of a quality standard such as GMP

Periodic evaluations are routine reviews and assessments of the quality standards of each drug product that are made to determine the need for changes in drug product specifications or manufacturing or control procedures

Auditors should not have direct responsibilities for the operations they review

Employees who are directly responsible for system under review normally perform periodic evaluations

Audit is the function of Quality assurance

Periodic evaluation is a function of Quality control department 

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Quality audit 

Periodic Evaluation 

To verify on a regular basis that a firms procedures and practices are in conformity with established SOPs and applicable GMPs 

Periodic Evaluation determine the need for change in product, specification or control procedures and implement it if necessary

Auditors reviewed Sops, Employee practices And behavior to see how well they follow established SOPs

It plays a primary role in Day-to-Day decision-making process used by QC unit

Report is prepared by Q.C personnel Quality control management personnel usually prepared Periodic evaluations

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Principle:- To evaluate the manufacturer’s

Compliance with GMP in all aspects of production and Quality control.

Designed to detect any shortcomings in the implementation of GMP and to recommend the necessary corrective actions

Performed routinely as well as on special occasions, e.g. in the case of product recalls or repeated rejections

 

4.Self Inspection

Items of Self inspection

Personnel Premises including personnel

facilities Maintenance of buildings and

equipment Storage of starting materials

and finished products Equipment Production and in-process

controls Quality control

To be Continued………

Documentation Sanitation and hygiene Validation and revalidation

programmes Calibration of instruments or

measurement systems Recall procedures Complaints management Labels control Results of previous self-inspections

and any corrective steps Taken

Conti.…

 

The quality audit system mainly classified in three different categories:

i    Internal Audits ii.    External Audits iii. Regulatory Audits

5.Types Of Quality Audit

Purpose of Internal audit:- To Ensure that adequate Quality systems are

maintained To asses compliance with the C-GMP’s and firms

standard operating procedure To achieve consistency between manufacturing

and testing facilities To identify problems internally and Correct

problems prior to a FDA inspection

i.Internal Audit

 

  Tier One Tier Two Tier Three

Carried out:- Staff of a section or department of company

Local Quality assurance Group

Corporate Compliance Group And External Consultant

Purpose:- Require Short time and Focusing on house keeping and documentation

Require Longer period and more focus on system than housekeeping

More focusing for asses the readiness of regulatory audit

Frequency:- More Less Less than tier two

Qualification:- Receive Some basic training

More exclusive training

Highly trained and experienced or specialist with the expert knowledge of GMP

Types Of Internal Audit

In a pharmaceutical facility for internal auditing, you require to check mainly two things namely

Activities carried out by different departments Documents maintained by these departments

Designing of the Internal Audit System

 

Constitute a small team of experts

Provide Initial training

Fix Audit schedule (Carried out at least once in Six months)

Report the Audit finding and report given to top management and Shows corrective actions

Repeat the audit as per preplanned Schedule

Implementing the Internal Audit Program

External Audit

Purpose of External Audit:-

Confidence in the partnership arrangement

Ensuring that requirements are understood

Enabling reduction of in-house QC testing of starting materials

Reducing the risk of failure

ii.External Audit

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Carried Out by a company on its vendors or sub

contractors

No legal requirement for to conduct audit

External auditors have experience of GMP and as well as regularly audited by their certification body

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Purpose of Regulatory audit:-

Networking and confidence-building between national inspection authorities

Development of quality systems

Work towards global harmonisation of GMP

iii.Regulatory Audit

Conti….

Carried out by regulatory bodies such as MCA(U.K),USFDA(USA) for manufacturing and supply of pharmaceutical product

Audits may be unannounced Failure of regulatory audit

withdrawal of a manufacturing or import/export license

After regulatory audit,a formal report will be delivered

For MCA:- verbal feedback report is given at the exit meeting

For USFDA:- Provides “Form 483”is given at the exit meeting

Conti….

6.Role of GMP Audits in Q.A And Q.C programmes

What is to be audited:- Auditors review

Compare master specifications against compendial and regulatory requirements

Verify the test data and validation testing Validation test reports are compared against raw

data Verify Corrective actions taken inreaction to audit

finding

SOPsEmployees Pracices and behaviour

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Assuring GMP compliance

Detecting Potential Problems

Effecting Programme improvement

Increasing management awareness

Benefits which are derived from Audits are given below:

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Assuring GMP Compliance

FDA conducts routine inspections of all pharmaceutical manufacturers to determine if manufacturing and control procedures conform to GMPs

FDA investigators make unannounced visits to the manufacturing facilities to examine facilities , equipments, personnel and records

Detecting Potential Problems

GMP audits find objectionmable condition that is

unknown to responsible production , QC ,QA or mangement personnel.

The auditor will see whether such actions are frequent or not .From this he can signal other GMP problems.

Effecting Programme Improvements

Changing SOPs Modifying maufacturing equipment or

procedure Upgrading equipment or procedure Improiving emplyee training programme Developing new or revised documentary system

Increasing Management Awareness

For any given audits there are two outcomes,either problems are found or not

If the problems are found , management takes an approprioate step to eliminate the problemn

An audit is not finding any objectionable conditions

Either there were no problems to be found Auditor failed to detect objectionble

condition that were actuaslly present

Key Elements i. Expectations and Philosophies ii. Audit Formats and Approaches Checklist format GMP regulation approach System analysis methods iii. Checklist written criteria and Standard

Operating Procedures iv. Planned periodic frequency for audit v. Specially trained personnel vi. Finding Written Audit reports

7.Elements of a Systemic Audit Program

Senior management establishes the fundamental expectations of audit

Upper level management must establish the realistic goals and objectives

Use of “ Formal Written Master Plan” approved by management

i.Expectations and Philosophies

Checklist format

GMP regulation approach

Systems analysis method

Manual GMP audit methods can be divided in to categories

ii.Audit Format And Approaches

Use checklist as GMP audit guides and reporting finding.

Series of questions or instructions are grouped in to logical order.

Blocks may be used to record answer and space may be provided to make comments.

Checklist Format

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Advantages:-

Simple, convenient and easy to use for any desired subjected area

Knowledgeable personnel may develop questions and guideline

Questions are in logical order that help auditor to detect problems

Report can be prepared in a minimum amount of time.

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Question may be interpreted in more than one way because of bias or hidden meaning

Solve the devising questions is not easy task Limited content

The amount and type of questions that are provided limited .

Not every issue will be covered Each auditor must apply sound judgment when

evaluating system.

Disadvantages:-Conti….

Subpart B: Organization and personnel Subpart C: Building and facilities Subpart D: Equipments Subpart E: Production and Processing Controls Subpart F: Production and Packaging control Subpart H: Holding and Distribution Subpart I: Lab controls Subpart J: Records and Reports Subpart K: Returned and Salvaged drug

The basic elements are derived from the following subpart of regulations

GMP Regulation Format

Likely to Affect the Quality Of the Product

These FDA investigators describe the organized method for determining of potential problem

Systemic Potential Problem Analysis

Need to be established defining which audit data or elements are to be considered in the assessment of program performance

Effective use of written criteria to ensure that conditions and practices remain under a suitable state of control

SOPs should establish

Formal written SOPs should fully describe the details for carrying out the various audit functions.

The responsibility for audit data reviewPersonnel responsible for recommendationsDecisions concerning corrective actions.

iii.Written Criteria And SOP

Each firm must establish the optimum time interval between audits based on several important factors like

Intended purposeObjectives, scope and depthPrior history of audit finding.

Two types of visit Can be done depending on the type of audit:-

Announced VisitUnannounced Audit

iv. Planned Periodic Frequency

Advanced notice is given before the audit.It is not persuasive for two reasons

Announced Visits:

The employee covers up the problem.

The person makes major adjustment in their behavior

Benefits :- Audit efficiency is improved from advance

notification Necessary records may be organized and

retrieved in the preparation for the audit. Key personnel become available

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To view conditions and practices that is normal or customary (representative) as possible.

For observing employees behavior as well as observation of equipments and facilities.

 

 Unannounced Audits

  Benefits :-

Allows observation of normal condition and practices

Conti….

The following personnel factors deserve systemic attention

Defining auditor Qualification

Documentation training skills and Experience.

Selecting audit teams

Maintaining auditor awareness levels

v. Specially Trained Personnel

Selected based

On their knowledgeExperience in manufacturing and QC

principles as well as years of first hand experience dealing with GMP matters.

Essential auditor skill is aware of

Firm’s SOPs and Knowledge Integrated by various departments.

Defining Auditor Qualification

Two formats

Scientific Principles Training under chemistry, engineering,

statistical and pharmaceutics

GMP GMP training may include the cumulative

knowledge from years of experience This knowledge comes from

Daily activities Formal training sessions

Documentation Training Skills And Experience

Limitations of Personnel audit Experience and knowledge, which is

individual.

Emphasize on familiar issues as well as particular area

Team is required for cover many different systems and large amount of data.

Composition of team will vary depending upon the nature and scope of the audit

Selecting Audit teams

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Leader is usually a senior auditor who has extensive knowledge of the firm’s operations and exhibit strong leadership qualities.

Team size depends upon

Firm size

Total no of products manufacturing and control system

Breath and depth of the audit.

The Audit objective

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Audit reports should contain complete details of the program detected.

Corrective action is taken to eliminate problems and to measure the overall adequacy of the audit program uses reports.

There are two important reporting phases:-

1) Preliminary reports during the audit2) Final report to the management

vi. Reporting Audit Finding

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Preliminary reports during the audit:

1) Benefits can be gained from having dialogues with employees

2) Finding is communicated with affected personnel.

3) Discussion may help the employees to learn why problems happened.

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Management must review the final reports and determine what steps need to be taken to eliminate deficiencies.

Management should sincerely encourage detection of problems and express appreciation for being able to improve quality operations.

The audit reports may be shared with manger supervisor who may discuss finding with employees.

The workers and supervisory personnel should be given the opportunity to explain their views and ideas about the audit findings.

Final report to the management

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References

Pharmaceutical Dosage forms:Parenteral medication,Revised and Expanded.Edited by Kenneth E.Avis,Herbert A.libermann and Leon Lachmann,Volume –3, Second edition ,

Page no:-363-420

Pharmaceutical Quality group mpnograph no:-5 (revised): Pharmaceutical Auditing , IQA2001,ISBN 0906810 68X

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Quality asuurance And Quality management in pharmaceutical Industry By Y.Anjaneyulu,R.Marayya,Pharma Book syndicate, Page no:-209-218

Provisional Guideline ON the inspection of the pharmaceutical manufacturers in: WHO Expert committee on specification for Pharmaceutical Preparations: 32ndreport,Geneva,WHO,1992,Annex-2(Who technical report seried. No:-823)

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