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