Dr. ajmal nasir

EQUIPMENT QUALIFICATION/VALIDATIO

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Dr.Ajmal Nasir Director Technical BF Biosciences 5 km Sundar Raiwind Road Raiwind LAHORE PAKISTAN

VALIDATION HELPS IN

Validation

Quality Assurance

Compliance Economics

VALIDATION HISTORY•1978 GMP include Validation

•1987 First Validation Guidance ( Equipment IQ)

•2000 New approaches/ Documents / Presentations

•2008 New Process validation Draft Guidance

(Equipment and Analytical Validation)

•2011 New Process Validation Guidance Issued

FDA 2011 GUIDANCE

•Definition VALIDATION (FDA – 2011)

• Collection and evaluation of data, from theprocess design stage throughout production, which

establishes scientific evidence that a process is capableof consistently delivering quality products.

Three stages of activities:• Stage 1 – Process Design – Development and scale-up

activities• Stage 2 – Process Qualification – Reproducible manufacturing

• Stage 3 – Continued Process Verification – Routine production1987 VALIDATION -- FOCUS IS PRIMARILY STAGE

2

2011 VALIDATION -- LIFECYCLE APPROACH

LIFE CYCLE APPROACH

STAGE 1

• DESIGN • UNDERSTAND

STAGE 2

• DEMONSTRATE

STAGE 3

• MONITOR• MAINTAIN

QUALIFICATION & FDA 2011 GUIDANCE

FDA does not define QUALIFICATION.

Qualification Considered as subset of validation,

Performed as a larger Validation Effort or in Support to Validation.

Equipment qualification provides documented evidence that the subject equipment has been installed per

specification (manufacturer's recommendations) and will attain and maintain critical process parameters repeatedly

and reliably.

VALIDATION VS QUALIFICATION

•Validation Documented evidence of a process for consistent predetermined outcome.

•QUALIFICATIONCorrect Equipment / Element As per Prerequisite / product design.

Performed on Individual Equipment or Element of the process to be validated

Tests conducted to establish specified outcome and verify characteristics to produce as per design.

VALIDATED

SYSTEM / PROCESS

QUALIFIED SUPPORT SYSTEMS

QUALIFIED MATERIALS

QUALIFIED / TRAINED

MANPOWER

QUALIFIED EQUIPMENT

PRE REQUISITES FOR VALIDATED SYSTEMS

USER REQUIREMEN

T SPECIFICATIO

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URS

DESIGN QUALIFICATIO

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D Q

INSTALLATION

QUALIFICATION

I Q

OPERATIONAL

QUALIFICATION

O Q

PERFORMANCE

QUALIFICATION

P Q

MAINTENANCE

CHANGE CONTROL

BEFORE PURCHAS

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BEFORE USE

AFTER USE

VENDORSSITE

OWNERS SITE

QUALIFICATION OVERVIEW

QUALIFICATION STEPS

VALIDATION TEAM URS RISK

ANALYSIS

EQUIPMENT

ORDERING

FAT PROTOCOLS EXECUTION DATA

ANALYSIS

CONCLUSION & EXECUTION

SUMMARY

EXECUTION SUMMARY APPROVAL

FINAL STATUS

VALIDATION TEAM

Assemble the Validation / Project Team• A multi-functional trained ,experienced team, led by a project leader.

• Project Leader To plan and oversee the validation activities. • Shall comprise of :

• Quality Assurance, • Engineering,• Manufacturing.• Quality Control• Technical Services• R&D Regulatory Affairs

• A Team Approach Will Guarantee Well Thought Out Qualification Processes .• Comprehensive Protocols .• Well Documented “Enhance Turn Over Package” Easy To Follow.

• Validation /Project Team Must:

• Determine what to verify & when.

• Identify Statistical tools & A clear metrics of

attributes

• Review, approve protocols , procedures & plans.

• Describe cogent acceptance/rejection criteria.

• Pinpoint essential documentation.

• Ascertain the split up of tasks and undertakings. • A extensive and formal Risk Analysis/ assessment for the correctness of the equipment for envisioned use .

• Compliance to MVP ,manage changes.

VALIDATION TEAM (Contd)

URS USER’S REQUIREMENT SPECIFICATIONS

•Define the intent through URS •Must be developed By Cross functional team.

•Clear definition of equipment •Clear concise &testable requirements• Formatted for easy access to the information•Approved by the Approving Authority.•Requirement statement referenced and not repeated.•Only spell requirement not the solution.•Avoid ambiguous and jargon words•No assumptions

•We shall define in Entirety:• Type of Power source ,•Supporting systems e.g. Pneumatics,•Controls, PLC ,H.M.I etc.• Exact materials of construction. (compatibility)• e.g. SS 316 L. SS 314, •Polymers, • specific coating on tools.

• Ergonomic details, Dimensions to fit in your area,.• Ease of Operation, Cleaning, maintenance• Intended Mechanical Speed

URS USER’S REQUIREMENT SPECIFICATIONS (Contd)

Sample URS..\PPA\JETT-GranulatorURS.doc

The risk assessment conclusion shall be part of project validation plan, individual protocols, or

any separate document

. CONDUCT A RISK ASSESSMENT

•Essential part of all validations.• Assessment by appropriate methods to the scope and nature of the validation project.

• Identify potential failure and fault modes of the equipment or system.

• Helps to define Proper Design,

• To gauge the relative level of validation testing and need for external safeguards.

RISK ANALYSIS

RISK SAMPLE

BASIS FOR PROTOCOLS

PROTOCOLS

PROCESS REQUIREME

NT

EQUIPMENT MANUAL

QUALITY PARAMETE

RS

PROTOCOL

PROTOCOL

APPROVAL

EXECUTION

APPROVAL

EXECUTION

EXECUTION

SUMMARY

APPROVAL

PROTOCOL

PREPARATION

EXECUTION

SIGN

OFF

ESSENTIAL DOCUMENTATION STEPS

DESIGN QUALIFICATION

• Based on URS defined by the user and on Product Design.

• Specifications reviewed and documented by competent

persons to ensure that equipment will satisfy all the

detailed specified requirements.

• A group of qualified persons to challenge the design if

built in- house or to select OFF the Shelf

equipment.

• D Q to verify that off-the-shelf equipment will fully

deliver the functionality detailed in the Design

Specification(URS) , and conform to the requirements

specified GMP guidelines.

DESIGN SPECS

FINALIZED

EQUIPMENT

ORDERING

PLAN

IQ, OQ ,PQ

Approved URS

FINANCIALANALYSIS

DQDesign

Qualification

IQ

Installation Qualification

OQOperational Qualification

PQPerformance Qualification

INSTALLATION QUALIFICATION

• To Verify that:

• Correct equipment has been received, installed as per plan and protocol.

• Equipment is complete and undamaged.• All parts, services, controls, gauges and other

components as per requirement.• Proper utilities connections.• Traceable Calibration of measuring, control and

indicating devices.• CONFIRMS Equipment materials& Finishes of

surfaces.• Out puts and Inputs are consistent to the

Design.• Equipment ,operators & materials are

COMFORTABLE..

OBJECTIVE To establish by objective evidence that the equipment is installed or modified according to specifications.

THIS CONFIRMS THAT AFTER INSTALLATION

EQUIPMENT IS IN ORDER.

THAT THE EQUIPMENT WILL OPERATE THE

WAY IT WAS DESIGNED

INSTALLATION QUALIFICATION

Installation Qualification (IQ) Evaluates Means Of Accommodating New Equipment And Testing Its

Materials.

Purpose Needs for the equipment to be installed

ScopeA new equipment or already installed equipment being installed after Modification or change.

Equipment/ System

Description

Function of the equipment , mode of operation, process or product for, and basic design and working principle .

Supplier• Brief Vendor description , certification

and safety feature verification

Equipment Components

• Brief description of major components .

• Ancillary equipment used in conjunction with the equipment being qualified should be identified as appropriate

SECTION REQUIREMENT/CONTENT

Utilities• Utilities required to operate the

equipment should be identified.

• Supporting Documentation

• Enlist Equipment Identification and operation documents.

• Engineering Turnover Packages, Purchase Orders, or Equipment Manuals

• Spare/Change Parts

• List down spare parts and change parts.

• Identify parts through part number / Internal code with clear definition

• Drawings• Verified Drawings as per Design shall

be part of IQ


Testing and Acceptance

Criteria

• Approved Acceptance criteria before execution.

• Installation Confirmation as per Vendor recommendation In case of deviation .

• Acceptance criteria based on proper justification & risk analysis

• Actual Reading and supporting documents to be part of protocol.

Discrepancies • Discrepancies must be described and Justified .

Summary and Conclusion

• Summarize IQ test results,• Demonstrate Correct Installation of

the equipment.• Provide a conclusion to spell out

Installation acceptable or Not


OPERATIONAL QUALIFICATION

• Verifies Equipment Operation as per Specifications.

• Challenging the Equipment Parameters.• Verifies equipment operates according to :•Specifications. •Within Working range ,•Rejection level In limits ,• Designed output •Designed energy consumption.

•OQ, at the very least, must include and/or address the items in next slides • Statistical tools should be applied to optimize equipment and process performance.


Purpose • State the equipment needs to be qualified

Scope• State whether the installation is for new

equipment or modifying previous qualified equipment

Equipment/System

Description

• Describe what the equipment does, how it is used, what process/products use it, and its basic design features

If above fully described in the IQ, then a reference to the IQ is acceptable


Operational Qualification

Pre-requisites

Verify :• All IQ tests have been completed

prior to execution of OQ• Any Deferred IQ is identified in a

protocol and Justified as non-critical prior to OQ testing .

Test Equipment Calibration Verification

• List of qualified test equipment.• Approved materials used in protocol

execution .• List calibration date and next due

date

Standard Operating

Procedures

Pre Approved, Implemented :• Operating, setup and/or cleaning

procedures• Maintenance Procedures.


Alarm/Control Challenges

• Identify and challenge critical alarms associated equipment/system.

• Systems integrated with other systems can be part of other protocols and challenged separately.

Operating Parameters

• Define and Verify the key and critical process parameters .

• Validate the operating ranges and acceptance criteria for each parameter.

Rationale and Sampling Locations

Provide rationale for:

Qualification approach taken

Sample size rationale

Selected test conditions

Critical parameters


Testing and Acceptance

Criteria

• Define the test range for each critical process parameter for Validation.

• Range shall “bracket” the operating range for security.

• Challenge process at the extremes of the critical process parameters wherever possible.

• Number of test runs statistically justified and linked to the complexity of the equipment

Test Result Documenta

tion

• Summarize test results and confirms the acceptance criteria

Discrepancies

• Discuss and justifies discrepancies

Summary and

Conclusion

• Summarize equipment OQ results and provide a conclusion on whether the equipment operation is acceptable

Section Requirement/Content

PERFORMANCE QUALIFICATIONPQ

• Verification of equipment Performance conferring to design specifications & URS .

• Reliable and reproducible Results Under normal production conditions in compliance to Performance Qualification protocol.

• Shall be performed for Justified Interval, long enough for consistent and closely controlled quality production.

• justify the Operational Run duration or period.

PQ PLAN ELEMENTS

1. Purpose

2. Scope

3. Equipment Description

4. Operational Specifications

5. Acceptance Criteria

6. Testing Results

7. Discrepancies/Corrective Actions

8. Conclusions/Final Report


• Performance Qualification (PQ) is performed after successful completion of the Installation qualification (IQ) and Operational Qualifications (OQ) .

• Performed on actual production batch size .

• Sample sizes are larger to have larger Data for analysis.

• The testing verifies that the performance specified in the Design Specification is being delivered.

• The PQ represents the final qualification of equipment or system. • This incorporates a range of testing to simulate process options and provide assurance that systems and operating documentation, are capable of subsequent process validation activities.

PQ ESTABLISH AND/OR CONFIRM :• Definition of performance criteria and test

procedures.

• Selection of critical parameters, with predefined specifications.

• • Determination of the test intervals, e.g.,

(a) - Everyday.(b) - Every time the system is used.(c) - Before, between and after a series of runs.

• Define corrective actions on what to do if the system does not meet the established criteria.


P P Q ?Process Performance Qualification The process performance qualification (PPQ) is the second element of Stage 2, process qualification. The PPQ combines the actual facility, utilities, equipment (each now qualified), and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches. A successful PPQ will confirm the process design and demonstrate that the commercial manufacturing process performs as expected.

Success at this stage signals an important milestone in the product lifecycle. A manufacturer must successfully complete PPQ before commencing commercial distribution of the drug product.16 The decision to begin commercial distribution should be supported by data from commercial-scale batches. Data from laboratory and pilot studies can provide additional assurance that the commercial manufacturing process performs as expected.

Except regulatory requirements regarding time specific intervals for periodic re-qualification, a validation assessment to be

completed for each change to determine and document for no potential validation impact and the validation status is maintained, including the possibility of requalification.

Requalification Review

The validation status of qualified equipment must be reviewed to determine whether it continues to operate

in A qualified state.

Change control determines requalification requirements to maintain the validated state.

RE QUALIFICATION

Required if Change in:

- Batch size (significant)

- Operating parameters

- Component / Materials specifications

- New accessories or components are added

to a qualified equipment

- Process changes that potentially can effect

Quality

PROTOCOL EXAMPLES

WHO

ISPE

THANKS Any Questions?

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Dr. ajmal nasir