1. EQUIPMENT QUALIFICATION/VALIDATION
Dr.Ajmal Nasir Director Technical BF Biosciences 5 km Sundar Raiwind Road Raiwind LAHORE PAKISTAN

2. VALIDATION HELPS IN
Validation
Quality Assurance
Compliance
Economics

3. VALIDATION HISTORY 1978 GMP include Validation
1987 First Validation Guidance ( Equipment IQ)
New approaches/ Documents / Presentations
New Process validation Draft Guidance
(Equipment and Analytical Validation)
New Process Validation Guidance Issued

4. 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
VALIDATION -- LIFECYCLE APPROACH

5. LIFE CYCLE APPROACH DESIGN UNDERSTAND DEMONSTRATE MONITOR MAINTAIN
STAGE 1
DESIGN
UNDERSTAND 2
DEMONSTRATE 3
MONITOR
MAINTAIN

6. 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.

7. 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.

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

9. 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

10. 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

11. 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.

12. 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.

13. 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

14. 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

15. 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

16. BASIS FOR PROTOCOLS PROCESS REQUIREMENT EQUIPMENT MANUAL
QUALITY PARAMETERS

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

18. 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.

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

20. Installation Qualification Operational QualificationDQ
Design Qualification IQ
Installation Qualification OQ
Operational Qualification PQ
Performance
Qualification

21. 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. .

22. 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

23. 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

24. 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

25. 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

26. 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.

27. 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

28. 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.

29. 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

30. 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

31. 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.

32. PQ PLAN ELEMENTS Purpose Scope Equipment Description
Operational Specifications
Acceptance Criteria
Testing Results
Discrepancies/Corrective Actions
Conclusions/Final Report

33. 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.

34. 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.

35. 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.

36. 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.   

37. 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

39. PROTOCOL EXAMPLES
WHO
ISPE

40. THANKS
Any Questions?