This document discusses equipment qualification using a lifecycle approach. It recommends qualifying equipment based on stages of design/understanding, demonstration, and monitoring/maintenance. The key points are: 1) Equipment qualification is vital for validation and FDA expectations have changed, 2) Qualification should use a lifecycle approach in three stages, 3) Qualification is not a one-time event but ongoing, 4) Principles like risk analysis and documentation are important, 5) Traditional IQ/OQ/PQ or ASTM E2500 approaches can be used, and 6) Documentation must be consistent, complete and retrievable. Model documents and a documentation hierarchy are also recommended.

1.
VALIDATION
BOOT
CAMP
#4
LIFECYCLE
APPROACH
TO
PHARMACEUTICAL
VALIDATION
–
PRINCIPLES,
IMPLEMENTATION,
AND
PRACTICE
EQUIPMENT QUALIFICATION –
LIFECYCLE APPROACH
Paul L. Pluta, PhD
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2. OUTLINE
I. Equipment Qualification – Lifecycle Approach
• Qualification approaches
• Documentation hierarchy
• Document outlines
II. Documentation problems
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3. EQUIPMENT QUALIFICATION – LIFECYCLE APPROACH
KEY POINTS SUMMARY
1. Equipment qualification is a vital part of validation.
2. New FDA process validation guidelines has changed expectations
for equipment qualification.
3. Approach equipment qualification by lifecycle approach stages
• Stage 1. Design / understand
• Stage 2. Demonstrate
• Stage 3. Monitor / maintain.
4. Equipment qualification must not be considered a one-time event.
5. Key validation principles identified -- Confirmation, risk analysis,
documentation, others.
6. Qualification options: IO/OQ/PQ or ASTM E2500.
7. Model documents recommended.
8. Documentation is vital: Consistency, content, good documentation
practices, and document retrieval.
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4. INTRODUCTION -- VALIDATION AND QUALIFICATION
PROCESS VALIDATION – PROCESS QUALIFICATION
PROCESS PERFORMANCE QUALIFICATION
Qualification Qualification
Unit
Equipment #1 Opera.on
HVAC
#1
Utilities
Equipment #2
Facilities
#2
Computers
Equipment #3
#3
Analytical methods validation
Cleaning process validation
Packaging process validation
PROCESS IS VALIDATED
ALL SUPPORTING EQUIPMENT, FACILITIES, UTILITIES, CONTROL SYSTEMS,
ANALYTICAL, ETC. MUST BE QUALIFIED.
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5. FDA PROCESS VALIDATION GUIDANCE 2011
Validation History
• 1978 – GMP includes Validation
• 1987 – First Validation Guidance
o Equipment IQ
• 2000 à New approaches / documents / presentations
• 2008 – New Process Validation draft guidance
o Equipment and analytical included
• 2011 – New Process Validation Guidance issued
FDA EXPECTATIONS FOR VALIDATION / QUALIFICATION
CONSIDER POTENTIAL APPLICATION TO EQUIPMENT
SAME AUDITORS – PHARMA, DEVICES, PROCESSES, EQUIPMENT
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6. Definition FDA – 2011
Definition: 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
1987 VALIDATION -- FOCUS IS PRIMARILY STAGE 2.
2011 VALIDATION -- LIFECYCLE APPROACH
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7. Medical Device Validation
Comparison to Pharma
• Device IQ = Pharma IQ / OQ / PQ
• Device OQ = Product R&D (Stage 1 development)
• Device PQ = Pharma PV
Reference: Device GHTF
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8. VALIDATION / QUALIFICATION PRINCIPLES
• Validation is confirmation
• Risk analysis determines everything
• Science and technical basis for design and development
• Lifecycle approach
– Understand, demonstrate, monitor and maintain
• Sampling and testing -- rationale and justification
• Pre-approved acceptance criteria
• Data-based judgments
• Documentation of above
• Document retrieval
• Maintain validation continuously
• Change control
APPLICATION TO EQUIPMENT QUALIFICATION
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9. VALIDATION IS CONFIRMATION
Successful validation is expected.
Do not initiate validation unless success is
expected.
Validation is not the final step in development,
installation, optimization, fine-tuning, or other
development activities.
Amendments, mistakes, failures scope changes,
etc. all have negative implications.
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10. RISK MANAGEMENT
Risk defines everything.
Test only critical equipment parameters in
validation. Risk level determines level of testing.
Test non-critical equipment parameters during
commissioning.
Document risk assessment.
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11. EQUIPMENT QUALIFICATION APPLICATIONS
Lifecycle approach
Risk analysis
Science and technical basis for design and development
Validation confirms equipment design and development
Sampling and testing -- rationale and justification – based on risk
Pre-approved acceptance criteria
Data-based judgments
Document everything – Retrieve documents
Maintain validation continuously throughout lifecycle -- based on risk
• Preventive maintenance
• Calibration
• Change control
DOES THIS MAKE SENSE?
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12. EQUIPMENT QUALIFICATION
Qualification approaches
• DQ / IQ / OQ / PQ (IQ for medical devices)
• ASTM E2500
Documentation hierarchy
Document outlines
• Model documents
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13. QUALIFICATION APPROACHES
DQ / IQ / OQ / PQ
Traditional qualification
DQ – Multiple functions and applications
• Purchasing document
• Equipment design document
Documents may be combined
• IQ, OQ, PQ
• IOQ, PQ
• IOQ
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14. DQ / IQ / OQ / PQ CONTENT
DQ – Design Qualification
• Equipment description
• Equipment design requirements
• Purchase / design specific requirements
IQ – Installation Qualification
• Components
• Drawings
• Operating manuals
• Product-contact material composition
• Surface area calculations (product contact equipment)
• Calibration
• Preventive maintenance
• Equivalence to other equipment
• Most difficult to clean locations
• Other
OQ – Operation Qualification
• Worst case / range parameter operation
PQ – Performance Qualification
• Integrated parameter operation with representative materials
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15. ISPE EQUIPMENT VALIDATION
User Requirements PQ
Specification
Functional Specification OQ
Design Specifications IQ
System Build
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16. EQUIPMENT QUALIFICATION LIFECYCLE
1. Capital request with design (DQ)
2. Equipment build
3. Factory Acceptance Test (FAT)
4. Site Acceptance Test (SAT)
5. Commissioning
6. IQ
7. OQ
8. PQ
9. Preventive Maintenance and Calibration
10. Change control
11. Decommissioning
CONSISTENT WITH STAGE APPROACH
DOCUMENTATION ON ALL
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17. EQUIPMENT QUALIFICATION
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
Test and document critical items only.
FAT, SAT, and Commissioning
Test and document non-critical items.
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18. ASTM E2500. Standard Guide for Specifications, Design, and
Verification of Pharmaceutical and Biopharmaceutical
Manufacturing Systems and Equipment
• Design Input
• Design Review
• Risk Mitigation
• Critical Control Parameters Define
• Acceptance Criteria
• Verification Testing
• Performance Testing
• GEP scope and QA scope have clear boundary
• Process, Product Quality and Patient Safety
• Quality by Design, Design Space and Continuous Improvement
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19. ASTM E2500
19

20. ASTM E2500
20

21. TRADITIONAL QUALIFICATION VS. E2500
Focused objective
Comprehensive approach
Includes risk analysis
Critical parameters
Less paperwork
• Same content
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22. DOCUMENTATION HIERARCHY
Company policy
Validation Master Plan
DQ
Design and development
SAT / FAC
Commissioning
Validation / Qualification Request / Plan
IQ /OQ /PQ Protocol / Results / Report
Post Validation Monitoring / Maintenance
Change control
Associated technical document (e.g., manuals, etc.)
Associated documents (e.g., training, HR)
Management Review
CONSISTENT LIFECYCLE APPROACH
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23. DOCUMENT OUTLINES
Validation Initiation
Validation Plan
IQ – Protocol and Results
OQ – Protocol and Results
PQ – Protocol and Results
IQ/OQ/PQ Report
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24. VALIDATION REQUEST OUTLINE
Objective of validation
Why needed?
Impact of validation
• Risk analysis
Why acceptable?
• Compliance to internal requirements, policies, engineering standards, etc.
• Regulatory impact (Prior approval, CBE, CBE30, etc.)
• Other systems or product impacted
• Procedure changes or other document changes
• Notifications to affected groups (internal, external, labs)
Validation plan -- Approach to accomplish validation
Above applicable to equipment and other qualification
HAVE MODEL DOCUMENTS AVAILABLE
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25. QUALIFCATION PLAN OUTLINE
Introduction
Technical information
Qualification strategy and testing
Qualification documentation
• List of required protocols, reports, procedures, etc.
• Administrative benefit
References
• List of reports and scientific references (including Stage 1
reports)
HAVE MODEL DOCUMENTS AVAILABLE
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26. PROTOCOL OUTLINE
Introduction
Equipment
Testing with justification
Sampling with justification
Sampling and data pages
Data treatment
Acceptance criteria with justification
HAVE MODEL DOCUMENTS AVAILABLE
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27. RESULTS OUTLINE
Introduction
Data sheets compiled
Data treatment
Results
Deviations, Non-conformances, etc.
Discussion
• “Results pass” is not sufficient.
Validation statement:
“Results indicate that ___ is validated / qualified.”
Post-validation plan
WRITE DISCUSSION SECTION FIRST – MOST IMPORTANT SECTION
HAVE MODEL DOCUMENTS AVAILABLE
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28. QUALIFICATION REPORT
Combined IQ / OQ / PQ results
Helpful in audit – total summary
“Cut and paste” results and conclusions sections
Consistency and completeness important
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29. REPORT FORMAT
• Introduction
• Key information from Validation Plan
• Supporting information
• Protocol #1 results – “Cut and paste”
• Protocol #2 results – “Cut and paste”
• Protocol #3 results – “Cut and paste”
• Protocol #n results – “Cut and paste”
• Write transitional narrative
• Project conclusions
• Validation statement
– “Results indicate that ______ is validated / qualified.”
HAVE MODEL DOCUMENTS AVAILABLE
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30. TEMPLATES vs. MODEL DOCUMENTS
Recommendation:
1. Prepare “perfect” document – make available as
needed
2. Assemble multiple documents from different
applications
3. Upgrade as needed
4. Documents available to technical writers
5. Validation Review Board maintain standards.
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31. DOCUMENTATION PROBLEMS
• Qualification statement: “________ is qualfied.”
• Documentation content
o Scientific and technical
o Compliance with policies/procedures/regulations
• Errors, mistakes, and omissions
o Sampling and data pages
o Equipment not ready to be qualified
• Original data consistency
o Documentation practices – original data
o Missing results
o Retrieval
• Documentation rules
• Others
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32. DOCUMENTATION –
THREE SIMPLE RULES
1. Clear, complete, concise, consistent
2. “Stand-alone” documents – written for the
reader
3. Short sentences and simple words
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33. SUMMARY
1. Equipment qualification is a vital part of validation.
2. New FDA process validation guidelines has changed expectations for
equipment qualification.
3. Approach equipment qualification by lifecycle approach stages
• Stage 1. Design / understand
• Stage 2. Demonstrate
• Stage 3. Monitor / maintain.
4. Equipment qualification must not be considered a one-time event.
5. Key validation principles identified -- Confirmation, risk analysis,
documentation, others.
6. Qualification options: IO/OQ/PQ or ASTM E2500 .
7. Documentation is vital: Consistency, content, good documentation
practices, and document retrieval.
8. Implementation strategies: Management support and document content.
9. Lifecycle change = Reorientation – Not a significant change.
33

34.
PAUL
L.
PLUTA,
PhD
Editor-­‐in-­‐Chief
Journal
of
Valida-on
Technology
Journal
of
GXP
Compliance
Advanstar
Communica.ons
Adjunct
Associate
Professor
University
of
Illinois
at
Chicago
(UIC)
College
of
Pharmacy
Chicago,
IL,
USA
PharmaceuJcal
industry
experience
Contact:
paul.pluta@comcast.net
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