Module 4

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Slide 1 of 28 January 2006
Qualification and
Validation
Basic Principles of GMP
Section 4
Module 4
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Slide 2 of 28 January 2006
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)
Module 4
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Slide 3 of 28 January 2006
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
Module 4
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Slide 4 of 28 January 2006
Qualification and Validation
Principle

Essential part of GMP
Manufacturer to identify what qualification and validation work is
required
Prove that critical aspects of work are controlled
Key elements of qualification and validation defined and
documented
4.1, 4.2, 4.8
Module 4
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Slide 5 of 28 January 2006
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)
Module 4
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Slide 6 of 28 January 2006
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)
Module 4
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Slide 7 of 28 January 2006
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)
Module 4
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Slide 8 of 28 January 2006
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 (OQ)
4.3(d)
Module 4
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Slide 9 of 28 January 2006
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)
Module 4
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Slide 10 of 28 January 2006
Qualification and Validation
Scope

Qualification and validation:
Applicable to any aspect of operation which may affect the quality of
the product
Directly or indirectly
Includes premises, facilities (utilities), equipment, processes
Includes significant changes
4.4
Module 4
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Slide 11 of 28 January 2006
Qualification and Validation
Principle

Qualification and validation should be done in accordance with an
ongoing programme
Initial qualification and validation
Annual review
Maintain continued validation status
Policy described in relevant documentation, e.g. quality manual, or
Validation Master Plan
4.5, 4.6
Module 4
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Slide 12 of 28 January 2006
Qualification and Validation
Types of Documentation

Validation Master Plan (VMP)
Validation protocols
Validation reports
Standard Operating Procedures (SOPs)

Module 4
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Slide 13 of 28 January 2006
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
Module 4
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Slide 14 of 28 January 2006
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
Module 4
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Slide 15 of 28 January 2006
Basic Principles of GMP


What are the qualification
and validation requirements
here for this piece of
equipment, as well as the step
in production?
Module 4
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Slide 16 of 28 January 2006
Annex 6
Qualification and Validation
WHO References

Good manufacturing practices (GMP): guidelines on the validation
of manufacturing processes
Validation of analytical procedures used in the examination of
pharmaceutical materials
Module 4
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Slide 17 of 28 January 2006
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)
Module 4
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Slide 18 of 28 January 2006
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
Module 4
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Slide 19 of 28 January 2006
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)
Module 4
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Slide 20 of 28 January 2006
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.

Module 4
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Slide 21 of 28 January 2006
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?
Module 4
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Slide 22 of 28 January 2006
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?
Module 4
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Slide 23 of 28 January 2006
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
Module 4
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Slide 24 of 28 January 2006
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

Module 4
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Slide 25 of 28 January 2006
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


Module 4
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Slide 26 of 28 January 2006
Qualification and Validation
Possible situation II

New product introduced into an existing tablet manufacturing
site, with 20 products already being produced
Process Cleaning
Training

Module 4
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Slide 27 of 28 January 2006
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
Module 4
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Slide 28 of 28 January 2006
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