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 [Link] 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