module 4 | slide 1 of 31 2012 qualification and validation basic principles of gmp section 4

Module 4 | Slide 1 of 31 2012

Qualification and Validation

Basic Principles of GMP

Section 4

Module 4 | Slide 2 of 31 2012

Qualification and ValidationQualification 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 | Slide 3 of 31 2012

Qualification and ValidationQualification 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 | Slide 4 of 31 2012

Qualification and ValidationQualification 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

Module 4 | Slide 5 of 31 2012

Qualification and ValidationQualification 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 | Slide 6 of 31 2012

Qualification and ValidationQualification and Validation

Scope

Documented evidence to prove that, e.g.PremisesSupporting 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 | Slide 7 of 31 2012

Qualification and ValidationQualification 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 | Slide 8 of 31 2012

Qualification and ValidationQualification 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)

Module 4 | Slide 9 of 31 2012

Qualification and ValidationQualification 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 | Slide 10 of 31 2012

Qualification and ValidationQualification and Validation

Scope

Qualification and validation:

Applicable to any aspect of operation which may affect the quality of the productDirectly 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

Module 4 | Slide 11 of 31 2012

Qualification and ValidationQualification and Validation

Principle

Qualification and validation should be done in accordance with an ongoing programmeInitial qualification and validationAnnual 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

Module 4 | Slide 12 of 31 2012

Qualification and ValidationQualification and Validation

Types of Documentation

Validation Master Plan (VMP)

Validation protocols

Validation reports

Standard Operating Procedures (SOPs)

Module 4 | Slide 13 of 31 2012

Qualification and ValidationQualification 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 | Slide 14 of 31 2012

Qualification and ValidationQualification and Validation

Importance:

Premises, utilities, equipment and processes

Critical importance and particular attention paid to validation of:Analytical test methodsAutomated systemsCleaning procedures

4.11

Module 4 | Slide 15 of 31 2012

Basic Principles of GMPBasic Principles of GMP

1. List qualification requirements for this piece of equipment.

2. Discuss aspects to be considered in validation during this processing stage.

Module 4 | Slide 16 of 31 2012

Qualification and ValidationQualification 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 | Slide 17 of 31 2012

Qualification and ValidationQualification 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 | Slide 18 of 31 2012

Qualification and ValidationQualification 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 | Slide 19 of 31 2012

Qualification and ValidationQualification 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

Module 4 | Slide 20 of 31 2012

Qualification and ValidationQualification 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”

Module 4 | Slide 21 of 31 2012

Qualification and ValidationQualification and Validation

Process design

Process qualification

Continued Process verification

Phase I

Phase II

Phase III

Module 4 | Slide 22 of 31 2012

Qualification and ValidationQualification 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

Module 4 | Slide 23 of 31 2012

Qualification and ValidationQualification and ValidationExample 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 | Slide 24 of 31 2012

Qualification and ValidationQualification 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 | Slide 25 of 31 2012

Qualification and ValidationQualification 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 | Slide 26 of 31 2012

Qualification and ValidationQualification 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 | Slide 27 of 31 2012

Qualification and ValidationQualification 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 | Slide 28 of 31 2012

Qualification and ValidationQualification 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 | Slide 29 of 31 2012

Qualification and ValidationQualification 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 | Slide 30 of 31 2012

Qualification and ValidationQualification 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 | Slide 31 of 31 2012

Qualification and ValidationQualification 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