Transcript Slide 1
Basic Principles of GMP
Qualification and
Validation
Section 4
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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)
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Qualification and Validation
Definitions
Glossary
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)
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Qualification and Validation
Principle
Qualification and Validation: Essential part of GMP
Manufacturer has to identify what qualification and
validation work is required.
4.1, 4.2, 4.8
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
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Qualification and Validation
Scope
4.3(a)
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
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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
4.3(b)
Also referred to as Installation Qualification (IQ)
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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)
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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 (PQ)
4.3(d)
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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)
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Qualification and Validation
Scope
Qualification and validation:
Applicable to any aspect of operation which may affect the
quality of the product
Directly or indirectly
Cover e.g. premises, facilities (utilities), equipment,
processes
4.4
In case of significant changes – consider the need for requalification or re-validation
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Qualification and Validation
Principle
Qualification and validation should be done in
accordance with an ongoing programme
Initial qualification and validation
Annual review (determine the need for revalidation)
4.5, 4.6
Ensure continued validation status is maintained
Policy described in relevant documentation, e.g.
quality manual, or Validation Master Plan
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Qualification and Validation
Types of Documentation
Validation Master Plan (VMP)
Validation protocols
Validation reports
Standard Operating Procedures (SOPs)
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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
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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
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Basic Principles of GMP
1. List qualification
requirements for this
piece of equipment.
2. Discuss aspects to
be considered in
validation during this
processing stage.
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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…
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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)
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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.
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Qualification 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
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Qualification 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”
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Qualification and Validation
Phase I
Process design
Process
qualification
Continued
Process
verification
Phase III
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Phase II
Qualification and Validation
WHO References
Supplementary guidelines on good manufacturing practices:
validation
… including details about
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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
Annex 4
Non-sterile process validation
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Qualification and Validation
Example of priorities for process validation
Type of process
New
Existing:
Requirement
Every new process before approval for routine
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)
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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?
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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?
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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
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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
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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
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Qualification and Validation
Possible situation – II
New product introduced into an existing tablet manufacturing
site, with 20 products already being produced
Process Cleaning
Training
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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
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Qualification and Validation
Possible situation – IV
An existing sterile suite producing 5 products that are terminally
sterilized
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Sterilizers
Ventilation and other environmental aspects
Equipment and process
Cleaning
Training
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