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
© WHO – PSM
Validation principles
Objectives
To review:

WHO validation definition

Philosophy of validation

Personnel requirements

Protocol requirements

DQ IQ OQ and PQ summary

Checklist for validation
© WHO – PSM
Validation
WHO validation definition

The documented act of proving that any
procedure, process, equipment, material,
activity or system actually leads to the
expected results.
© WHO – PSM
Validation
The VMP

The VMP provides a summary of the
company’s philosophy, policy, intentions and
approach to validation.
© WHO – PSM
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
© WHO – PSM
Validation
Quality is designed and built
into the
process/method/premises
Functionality, consistency and repeatability
is confirmed by
validation
© WHO – PSM
Validation
Validation as such
does
not improve the process
but it
confirms
and assures
that the process
Has
It
It
been well developed
is well maintained
operates as it should
© WHO – PSM
Validation
Advantages of validation:
During
the process the knowledge of process increases
Assures
the repeatability of the process
Assures
Assures
the fluency of production
that the product is continuously according to the
marketing authorisation
Decreases
Decreases
the risk of the manufacturing problems
the expenses caused by the failures in production
Decreases
the risks of failing in GMP
Decreases
the expenses of the every day production even
though the validation itself will create expenses
© WHO – PSM
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
© WHO – PSM
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
© WHO – PSM
WBS/Validation of clean area
VALIDATION
Clean area
Premises
- HVAC System
- LAF Units
- Cold Storage
- Env. Monitoring
- Facility Cleaning
- Transfer hatches
- Verifi. of classific.
Aseptic
Processing
- Media Fills
Utility
Systems
Manufacturing
Support Syst.
- Water systems
- Plant Steam
- Pure/Clean Steam
- Process Gases
- Sterilizers
- Depyrogenators
- SIP Systems
- CIP Systems
- Washing
- Waste Systems
- Fermentors
- Scales
- Incubators
- Filtration Units
- Filling Equipment
- Computerised
systems
In-Process
Control
Personnel
Training
Packaging &
Labeling
- Packaging
- Labeling
- Process Measurem.
- Visual Inspection
- Label Control
- Sampling
Equipment
- GMP
- Gpwning valid..
- SOPs
- Equipment
- Processes
© WHO – PSM
Manufacturing
Processes
- Fermentation
- Separation
- Purification
- Filtration
- Filling
Analytical
Methods
- Chemical - Cleaning valid
- Physical - Sterility tests
- Biological - Stability
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
© WHO – PSM
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
© WHO – PSM
Validation
© WHO – PSM
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
© WHO – PSM
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
© WHO – PSM
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
© WHO – PSM
Validation
Summary
cont…
Validation - Logical entity:
 protocol +
 procedure +
 report
© WHO – PSM