WHO GMP training lesson about Qualification and validation

1. Module 4 | Slide 1 of 31 2012
Qualification and
Validation
Basic Principles of GMP
Section 4

2. Module 4 | Slide 2 of 31 2012
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. Module 4 | Slide 3 of 31 2012
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. Module 4 | Slide 4 of 31 2012
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. Module 4 | Slide 5 of 31 2012
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. Module 4 | Slide 6 of 31 2012
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. Module 4 | Slide 7 of 31 2012
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. Module 4 | Slide 8 of 31 2012
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. Module 4 | Slide 9 of 31 2012
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. Module 4 | Slide 10 of 31 2012
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. Module 4 | Slide 11 of 31 2012
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. Module 4 | Slide 12 of 31 2012
Qualification and Validation
Types of Documentation
Validation Master Plan (VMP)
Validation protocols
Validation reports
Standard Operating Procedures (SOPs)

13. Module 4 | Slide 13 of 31 2012
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. Module 4 | Slide 14 of 31 2012
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. Module 4 | Slide 15 of 31 2012
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. Module 4 | Slide 16 of 31 2012
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. Module 4 | Slide 17 of 31 2012
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. Module 4 | Slide 18 of 31 2012
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. Module 4 | Slide 19 of 31 2012
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. Module 4 | Slide 20 of 31 2012
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. Module 4 | Slide 21 of 31 2012
Qualification and Validation
Process design
Process
qualification
Continued
Process
verification
Phase I
Phase II
Phase III

22. Module 4 | Slide 22 of 31 2012
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. Module 4 | Slide 23 of 31 2012
Qualification and Validation
Example of priorities for process validation
Type of process Requirement
 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. Module 4 | Slide 24 of 31 2012
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. Module 4 | Slide 25 of 31 2012
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. Module 4 | Slide 26 of 31 2012
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. Module 4 | Slide 27 of 31 2012
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. Module 4 | Slide 28 of 31 2012
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. Module 4 | Slide 29 of 31 2012
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. Module 4 | Slide 30 of 31 2012
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. Module 4 | Slide 31 of 31 2012
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