Basic Principles of GMP

Validation

Module 4 Slide 1 of 23 WHO - EDM

 Validation
Objectives

To review the definition and types of validation

To understand the requirements for
documentation and key stages in the process
of validation
To consider models for process validation

Module 4 Slide 2 of 23 WHO - EDM

 Validation
Definition
Validation is the documented act of proving
that any procedure, process, equipment,
material, activity or system actually leads to
the expected result

Module 4 Slide 3 of 23 WHO - EDM

 Validation
Essential Part of GMP
Predetermined protocols
Written reports
Processes and procedures
Periodic revalidation
Specific attention:
processing
testing
cleaning

Module 4 Slide 4 of 23 WHO - EDM

 Validation
WHO References

Good manufacturing practices: guidelines on

the validation of manufacturing processes

Validation of analytical procedures used in the

examination of pharmaceutical materials

Annex 6

Module 4 Slide 5 of 23 WHO - EDM

 Validation
Types of Process Validation
Experimental approach
Prospective validation
Concurrent validation
Analysis of historical data
Retrospective validation
Revalidation
Periodic revalidation
Revalidation after change

Module 4 Slide 6 of 23 WHO - EDM

 Validation
Stages of Validation

Design qualification (DQ)

Installation qualification (IQ)
Operational qualification (OQ)
Performance qualification (PQ)

Module 4 Slide 7 of 23 WHO - EDM

 Validation
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 Slide 8 of 23 WHO - EDM

 Validation
Types of Documentation

Validation Master Plan (VMP)

Validation protocols (VP)
Validation reports (VR)
Standard Operating Procedures (SOPs)

Module 4 Slide 9 of 23 WHO - EDM

 Validation
The Validation Master Plan could consist of:
Approval page and table of contents
Introduction and objectives
Facility and process description
Personnel, planning and scheduling
Responsibilities of committee members
Process control aspects
Equipment, apparatus, processes and systems to be validated
Acceptance criteria
Documentation e.g.validation protocols and reports
SOPs
Training requirements

Module 4 Slide 10 of 23 WHO - EDM

 Validation
Protocol
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

Module 4 Slide 11 of 23 WHO - EDM

 Validation
Report
Title
Objective of the study
Refer to the protocol
Details of material
Equipment
Programmes and cycles use
Details of procedure and test methods

Module 4 Slide 12 of 23 WHO - EDM

 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 Slide 13 of 23 WHO - EDM

 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 to
have faced when the company drafted these
documents?

Module 4 Slide 14 of 23 WHO - EDM

 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 Slide 15 of 23 WHO - EDM

 Validation
WHO Model for
Validation Protocol and Report - I

Part 1 Purpose and prerequisites

Part 2 Presentation of the process
Part 3 Validation protocol

Module 4 Slide 16 of 23 WHO - EDM

 Validation
WHO Model for
Validation Protocol and Report - II

Part 4 Installation qualification

Part 5 Qualification protocol/report
Part 6 Product characteristics

Module 4 Slide 17 of 23 WHO - EDM

 Validation
WHO Model for
Validation Protocol and Report - III

Part 7 Evaluation
Part 8 Certification
Part 9 Summary

Module 4 Slide 18 of 23 WHO - EDM

 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 Slide 19 of 23 WHO - EDM

 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 Slide 20 of 23 WHO - EDM

 Validation
Possible situation II

New product introduced into an existing tablet

manufacturing site, with 20 products already
being produced
Process Cleaning
Training

Module 4 Slide 21 of 23 WHO - EDM

 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 Slide 22 of 23 WHO - EDM

 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

Module 4 Slide 23 of 23 WHO - EDM