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•2008 New Process validation Draft Guidance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
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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
E
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
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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
SECTION REQUIREMENT/CONTENT
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
SECTION REQUIREMENT/CONTENT
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.
SECTION REQUIREMENT/CONTENT
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
SECTION REQUIREMENT/CONTENT
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.
SECTION REQUIREMENT/CONTENT
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
SECTION REQUIREMENT/CONTENT
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 QUALIFICATIONPQ
• 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.
PERFORMANCE QUALIFICATIONPQ
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?