Supplementary Training modules on

Good Manufacturing Practices

Validations –part 2
Pharmaceutical Quality,
Good manufacturing Practice &
Bioequivalence
Kiev, Ukraine
3 - 7 October 2005

Maija Hietava
M.Sci.Pharm
Quality Assurance and Safety: Medicines, Medicines Policy and Standards,
Health Technology and Pharmaceuticals Cluster
Tel: +41.22.791.3598 Fax: +41.22.791.4730
World Health Organization
E-mail: hietavam@who.int
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 Validation principles
Objectives
To review:
 WHO validation definition
 Philosophy of validation
 Personnel requirements
 Protocol requirements
 DQ IQ OQ and PQ summary
 Checklist for validation

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 Validation
WHO validation definition
 The documented act of proving that any
procedure, process, equipment, material,
activity or system actually leads to the
expected results.

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 Validation
The VMP
 The VMP provides a summary of the
company’s philosophy, policy, intentions and
approach to validation.

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 Validation
The WHO GMP Guidelines state:
Validation studies are an essential part of good
manufacturing practice and should be
conducted in accordance with predefined
protocols.
 written report and conclusion
 process and procedures
 processing
 testing
 cleaning procedures

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 Validation
Quality is designed and built
into the
process/method/premises

Functionality, consistency and repeatability

is confirmed by

validation
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 Validation
Validation as such
does not improve the process
but it
confirms and assures
that the process
Has been well developed
It is well maintained
It operates as it should

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 Validation
Advantages of validation:
During the process the knowledge of process increases
Assures the repeatability of the process
Assures the fluency of production
Assures that the product is continuously according to the
marketing authorisation
Decreases the risk of the manufacturing problems
Decreases the expenses caused by the failures in production
Decreases the risks of failing in GMP
Decreasesthe expenses of the every day production even
though the validation itself will create expenses

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 Validation
Personnel - Validation team members
 Quality Assurance
 Engineering
 Manufacturing
 Other disciplines may be involved depending on
the product and process:
 laboratory, technical services
 research and development, regulatory affairs
 clinical
 chemical engineering
 purchasing/planning

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 Validation
Protocol development (1)
 Identification of process
 Objective and measurable criteria
 Length and duration of the validation
 Shifts, equipment
 Identification and quality of utilities
 Identification of operators and operator training
and qualification

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WBS/Validation of clean area
VALIDATION

Clean area Utility Manufacturing Manufacturing

Equipment
Premises Systems Support Syst. Processes
- HVAC System - Water systems - Sterilizers - Fermentors - Fermentation
- LAF Units - Plant Steam - Depyrogenators - Scales - Separation
- Cold Storage - Pure/Clean Steam - SIP Systems - Incubators - Purification
- Env. Monitoring - Process Gases - CIP Systems - Filtration Units - Filtration
- Facility Cleaning - Washing - Filling Equipment - Filling
- Transfer hatches - Waste Systems - Computerised
- Verifi. of classific. systems

Aseptic Packaging & In-Process Personnel Analytical

Processing Labeling Control Training Methods
- Media Fills - Packaging - Process Measurem. - GMP - Chemical - Cleaning valid
- Labeling - Visual Inspection - Gpwning valid.. - Physical - Sterility tests
- Label Control - SOPs - Biological - Stability
- Sampling - Equipment
- Processes
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 Validation
Protocol development (2)
 Complete description of the process
 Relevant specifications and tests
 Samples and sampling methods
 Special controls or conditions
 Process parameters to be monitored
 Methods for controlling and monitoring

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 Validation
Protocol development (3)
 Objective and subjective criteria used to evaluate
the product
 Definition of non-conformance
 Statistical methods
 Maintenance and repairs
 Criteria for revalidation
 Criteria for change control

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Validation

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 Validation
GMP Inspector’s check list for validation (1)
Check that the manufacturer has:
 A VMP and multi-functional team for validation
 Planned approach , defined requirements
 Identified and described processes
 Analyse the amount of validation work to perform

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 Validation
GMP Inspector’s check list for validation (2)
Check that the manufacturer has:
 Selected methods and tools for validation
 Created protocols
 Performed DQ, IQ, OQ, PQ and documented results
 Exerted change control, set revalidation time

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 Validation
Summary
Validation
 A quality tool that makes lot of sense
 A prevention-based activity= important part of quality
building process
 Expensive in the beginning later will "save the money
back"
 In danger of becoming overwhelming
 Risk-based assessment of what needs to be validated or
verified
 The process must be under control/validation as such
does not improve the process
 Logical entity: protocol + procedure + report

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 Validation
Summary cont…

Validation - Logical entity:

 protocol +
 procedure +
 report

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