Module 4 | Slide 1 of 28 January 2006
Qualification and Validation
Basic Principles of GMP
Section 4
Module 4 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Slide 15 of 28 January 2006
Basic Principles of GMPBasic 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 | 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 | Slide 17 of 28 January 2006
Qualification 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 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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