Qualification and Validation

1. Basic Principles of GMP Qualification and Validation Section 4

2. Qualification and Validation Objectives • To review basic aspects of qualification and validation • To understand the scope of qualification and validation • Introduction to documentation associated with validation (See also Supplementary Training Module on Validation)

3. Qualification and Validation Definitions Validation • Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system actually leads to the expected results Qualification • Action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results (Validation usually incorporates the concept of qualification) Glossary

4. Qualification and Validation Principle • Qualification and Validation: Essential part of GMP • Manufacturer has to identify what qualification and validation work is required. • Provides proof that critical aspects of work are controlled and provide documented evidence • Key elements of qualification and validation defined and documented: Policy and approach: VMP 4.1, 4.2, 4.8

5. Qualification and Validation Scope • Documented evidence to prove that, e.g. • Premises • Supporting utilities • Equipment have been designed in accordance with GMP • Also referred to as Design Qualification (DQ) where appropriate 4.3(a)

6. Qualification and Validation Scope • Documented evidence to prove that, e.g. • Premises • Supporting utilities • Equipment have been built and installed in accordance with their design specifications • Also referred to as Installation Qualification (IQ) 4.3(b)

7. Qualification and Validation Scope • Documented evidence to prove that, e.g. • Supporting utilities • Equipment operate in accordance with their design specifications • Also referred to as Operational Qualification (OQ) 4.3(c)

8. Qualification and Validation Scope • Documented evidence to prove that, e.g. • Supporting utilities • Equipment perform consistently in accordance with their design specifications – see also next slide on PV • Also referred to as Performance Qualification (PQ) 4.3(d)

9. Qualification and Validation Scope • Documented evidence to prove that: • A specific process will consistently produce a product meeting its predetermined specifications and quality attributes • Also referred to as Process Validation (PV) 4.3(d)

10. Qualification and Validation Scope Qualification and validation: • Applicable to any aspect of operation which may affect the quality of the product • Directly or indirectly • Cover e.g. premises, facilities (utilities), equipment, processes • In case of significant changes – consider the need for re-qualification or re-validation 4.4

11. Qualification and Validation Principle • Qualification and validation should be done in accordance with an ongoing programme • Initial qualification and validation • Annual review (determine the need for re-validation) • Ensure continued validation status is maintained • Policy described in relevant documentation, e.g. quality manual, or Validation Master Plan 4.5, 4.6

12. Qualification and Validation Types of Documentation • Validation Master Plan (VMP) • Validation protocols • Validation reports • Standard Operating Procedures (SOPs)

13. Qualification and Validation Documentation • Clearly defines responsibility of performing validation • Conducted in accordance with predefined, approved validation protocols • Recorded results and conclusions presented in written validation reports – prepared and stored • Processes and procedures should be established on the basis of these results 4.7 – 4.10

14. Qualification and Validation Importance: • Premises, utilities, equipment and processes • Critical importance and particular attention paid to validation of: • Analytical test methods • Automated systems • Cleaning procedures 4.11

15. Basic Principles of GMP 1. List qualification requirements for this piece of equipment. 2. Discuss aspects to be considered in validation during this processing stage.

16. Qualification and Validation • The Validation Master Plan may contain elements (and policy) such as: • Approval page and table of contents • Introduction and objectives • Facility and process description • Personnel, planning and scheduling • Responsibilities of validation team members • Process control aspects • Equipment, apparatus, processes and systems qualified, validated – and to be qualified or validated • Acceptance criteria • Documentation, e.g.validation protocols and reports • SOPs • Training requirements and other elements…

17. Qualification and Validation • A qualification or validation protocol may contain: • Objectives of the validation and qualification study • Site of the study • Responsible personnel • Description of the equipment • SOPs • Standards • Criteria for the relevant products and processes (See WHO formats (handouts) as part of training material)

18. Qualification and Validation • A qualification or validation report should reflect the elements of the protocol, and may contain elements such as: • Title • Objective of the study • Reference to the protocol • Details of materials, equipment, instruments, personnel • Programmes and cycles used • Details of procedure and test methods … etc.

19. Qualification and Validation • New approaches recommend that manufacturers should perform a risk assessment as part of their approach to validation • Risk assessment can be useful in: • Identifying the need for qualification, or the extent and or scope of qualification (e.g. utilities and equipment) • areas of focus in process validation • Cleaning validation

20. Qualification and Validation • There is currently a move to change the approach to qualification and validation. The principles remain however the same. • US and EU guidance now focus on “Process qualification” which covers the complete lifecycle of a products with additional focus on product design • Three Phases are identified that cover “process design, process qualification” and “continued process verification”

21. Qualification and Validation Phase I Process design Process qualification Phase II Continued Process verification Phase III

22. Qualification and Validation WHO References Supplementary guidelines on good manufacturing practices: validation … including details about • Validation of heating, ventilation and air-conditioning systems • Validation of water systems for pharmaceutical use • Cleaning validation • Analytical method validation • Validation of computerized systems • Qualification of systems and equipment • Non-sterile process validation Annex 4

23. Qualification and Validation Example of priorities for process validation Type of processRequirement • New Every new process before approval for routine • Existing: • Sterile products All processes affecting the sterility, and manufacturing environment including sterilization stage • Non-sterile Low dose tablets and capsules: mixing and granulation; content uniformity (and other parameters) Other tablets and capsules: uniformity of mass (and other parameters)

24. Qualification and Validation Group Session 1: Option 1 • From your experience of factory inspections, what progress has been made in introducing validation in your country? • What are the major obstacles and how can they be overcome?

25. Qualification and Validation Group Session 1: Option 2 • List some documents related to validation, that you expect to find at a manufacturing site • Identify aspects in each document that you would evaluate or assess • What problems do you anticipate the company faced when it prepared these documents?

26. Qualification and Validation Possible Issues • Lack of time • Lack of personnel • Lack of experience and knowledge • Changes to the process • Prospective versus retrospective validation • Lack of documentation infrastructure • Lack of implementation of validation • Poorly designed documents

27. Qualification and Validation Group Session 2 • List the aspects that you will evaluate when assessing the validation for the project that your group has been given • Identify the critical parameters that should have been evaluated by the manufacturer • List the tests to be carried out and comment on the acceptance criteria to be set

28. Qualification and Validation Possible situation – I • Refurbishment of a liquids department, producing a single product on an established site with an existing purified water system • Ventilation system • Equipment and process • Training

29. Qualification and Validation Possible situation – II • New product introduced into an existing tablet manufacturing site, with 20 products already being produced • Process Cleaning • Training

30. Qualification and Validation Possible situation – III • A new liquids manufacturing building on an existing site which will produce 2 products • Ventilation • Equipment and process • Cleaning • Training

31. Qualification and Validation Possible situation – IV • An existing sterile suite producing 5 products that are terminally sterilized • Sterilizers • Ventilation and other environmental aspects • Equipment and process • Cleaning • Training