EQUIPMENT QUALIFICATION/VALIDATION 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First Validation Guidance ( Equipment IQ) 2000 New approaches/ Documents / Presentations 2008 New Process validation Draft Guidance (Equipment and Analytical Validation) 2011 New Process Validation Guidance Issued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 the process design stage throughout production, which establishes scientific evidence that a process is capable of 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 production VALIDATION -- FOCUS IS PRIMARILY STAGE 2 2011 VALIDATION -- LIFECYCLE APPROACH

LIFE CYCLE APPROACH DESIGN UNDERSTAND DEMONSTRATE MONITOR MAINTAIN STAGE 1 DESIGN UNDERSTAND 2 DEMONSTRATE 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 Documented evidence of a process for consistent predetermined outcome. QUALIFICATION Correct 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.

PRE REQUISITES FOR VALIDATED SYSTEMS VALIDATED SYSTEM / PROCESS QUALIFIED SUPPORT SYSTEMS QUALIFIED MATERIALS QUALIFIED / TRAINED MANPOWER QUALIFIED EQUIPMENT

QUALIFICATION OVERVIEW USER REQUIREMENT SPECIFICATION URS DESIGN QUALIFICATION D Q INSTALLATION QUALIFICATION I Q OPERATIONAL QUALIFICATION O Q PERFORMANCE QUALIFICATION P Q MAINTENANCE VENDORS SITE OWNERS SITE BEFORE PURCHASE BEFORE USE AFTER USE CHANGE CONTROL

CONCLUSION & EXECUTION SUMMARY EXECUTION SUMMARY APPROVAL 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 TEAM (Contd) 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.

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

USER’S REQUIREMENT SPECIFICATIONS (Contd) URS USER’S REQUIREMENT SPECIFICATIONS (Contd) 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 Sample URS..\PPA\JETT-GranulatorURS.doc

RISK ANALYSIS Essential part of all validations. . 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.   The risk assessment conclusion shall be part of project validation plan, individual protocols, or any separate document RISK SAMPLE

BASIS FOR PROTOCOLS PROCESS REQUIREMENT EQUIPMENT MANUAL QUALITY PARAMETERS

ESSENTIAL DOCUMENTATION STEPS PROTOCOL PROTOCOL APPROVAL EXECUTION APPROVAL EXECUTION EXECUTION SUMMARY APPROVAL PROTOCOL PREPARATION SIGN OFF

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 Approved URS DESIGN SPECS FINALIZED EQUIPMENT ORDERING PLAN IQ, OQ ,PQ FINANCIAL ANALYSIS

Installation Qualification Operational Qualification DQ Design Qualification IQ Installation Qualification OQ Operational Qualification PQ Performance Qualification

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

INSTALLATION QUALIFICATION Installation Qualification (IQ) Evaluates Means Of Accommodating New Equipment And Testing Its Materials. THIS CONFIRMS THAT AFTER INSTALLATION EQUIPMENT IS IN ORDER. THAT THE EQUIPMENT WILL OPERATE THE WAY IT WAS DESIGNED

Equipment/ System Description SECTION REQUIREMENT/CONTENT Purpose Needs for the equipment to be installed Scope A 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 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

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.

Equipment/System Description SECTION REQUIREMENT/CONTENT 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.

Alarm/Control Challenges Rationale and Sampling Locations 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

Testing and Acceptance Criteria 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 Documentation 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

PERFORMANCE QUALIFICATION PQ 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 Purpose Scope Equipment Description Operational Specifications Acceptance Criteria Testing Results Discrepancies/Corrective Actions Conclusions/Final Report

PERFORMANCE QUALIFICATION PQ 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.

PERFORMANCE QUALIFICATION PQ 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.

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. 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.   

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?