By: Dr. Mariam Zewail
Do you remember
what is GMP ??
GMP is a system for ensuring that
products are consistently produced
and controlled according to quality
standards.
GMP
Pharmaceutical
manufacturer
Principles
&
protocols
Product
with
quality
GMP is a preventive
action???
GMP is designed to minimize the risks
involved in any pharmaceutical production
that can not be eliminated through testing
the final product.
Lecture outline
 Definition of validation.
 Key points of validation.
 When should be validation performed.
 Advantages or objectives of validation.
 Validation responsibility.
 Validation and qualification.
 Process validation and its types.
Validation : Definition
WHO validation definition
The documented act of proving that any procedure,
process, equipment, material, activity, or system actually
leads to the expected results.
Validation is the establishment of documented evidence
that a system does what it is supposed to do.
Validation : Definition
There are three key points of validation:
1. The evidence must be documented.
(The results of the validation must be recorded).
2. Validation applies to several aspects of manufacturing,
including e.g. process development, materials, personnel
and equipment).
3. It should demonstrate that the system does what is
expected of it.
Validation (WHY??)
ADVANTAGES
•
•
•
•
•
Gives consistent product quality.
Processes become independent of personnel.
It gives confidence to employees and to customer.
It minimizes incidences of re-processing
It increases productivity.
When validation should be
performed??
Validation should be performed :
• For new premises, equipment, utilities, systems,
processes and procedures.
• At periodic intervals.
• When major changes have been done.
Validation Responsibility
Validation team consist of members from :
Responsible Department
Manufacturing
QA
QC
Responsible Authorities
Production manger
QA manager
QC manager
R&D
Maintenance manager
Important to ensure the validation of:
Production Process
Identification of critical
points of the
production process.
Analytical method
(Testing)
validated or verified
before used for routine
testing
Cleaning
Different products can
be manufactured on
the same equipment
Documented evidence which provide a high
degree of assurance that a specific process will
consistently result in a product that meets its
pre determined specifications and quality
characteristics.
Types of process
validation ??
•
•
•
•
Prospective validation.
Concurrent validation.
Retrospective validation.
Revalidation.
Types of process validation
• Prospective validation.
Based on evidence obtained through testing before operation.
• Concurrent validation.
Based on evidence obtained through testing during or upon
operation.
• Retrospective validation.(Statistical evaluation of old
records.)
Based on evaluation of past experience of production on the
condition that composition, procedures and equipment remain
unchanged.
• Revalidation
Repeated validation of an approved process to ensure continued
compliance with established requirements.
Types of process validation
Prospective validation
o It is carried out during the development stage.
o It includes the division of the production process
into separate steps, and the analysis of
potentially critical points in the manufacturing
process e.g. mixing times, or temperature.
o Trials are carried out in which these steps and
critical points are simulated and the effect on
the process is assessed.
Types of process validation
Concurrent validation
o It is carried out during normal production.
o It requires a full understanding of the process
based on prospective work.
o It involves very close and intensified monitoring
of the steps and critical points in at least the
first three production-scale batches.
Types of process validation
Retrospective validation
o It includes trend analysis on test results and a close
examination of all recorded process deviations.
o It is important to analyze 10 to 25 batches
manufactured over a period of 12 months to provide
a statistically significant picture.
It is not the preferred method of validation and
should be used in exceptional cases only.
Types of process validation
Revalidation
Changes requiring revalidation should be defined in the
validation plan and may include:
o changes in starting materials (including physical
properties, such as density, viscosity or particle size
distribution that may affect the process or product);
o Transfer of processes to a different site (including change
of facilities and installations which influence the process);
o Changes of primary packaging material (e.g. substituting
plastic for glass);
Types of process validation
Revalidation
Changes requiring revalidation should be defined in the
validation plan and may include (cont.):
o Changes in the manufacturing process (e.g. mixing times
or drying temperatures);
o Changes in the equipment (e.g. addition of automatic
detection systems, installation of new equipment, major
revisions to machinery or apparatus and breakdowns);
o Production area and support system changes (e.g.
rearrangement of areas, or a new water treatment
method).
Types of process validation
Revalidation
• Changes of equipment which involve
the replacement of equipment on a
“like-for-like”
basis
would
not
normally require a revalidation
• For example, installation of a new
centrifugal pump to replace an older
model would not necessarily require
revalidation
Types of Process
Validation
• Protocol
preparation
• During the
development
stage
Prospective
validation
Concurrent
validation
• During
production
Revalidation
• Analysis of
historical
data
Retrospectiv
e validation
• Periodic
revalidatio
n
• Revalidatio
n after
change
Types of Process Validation
Qualification or validation?
Qualification or validation?
Qualification or validation?
Example
You qualify an autoclave, whereas you validate
a sterilization process.
Stages of qualification
There are different stages of qualification that are
generally applied to projects such as premises,
equipment and supporting systems such as water supply
systems, Heating, Ventilation and Air Conditioning and
other systems.
1. Design qualification
(DQ)
2. Installation qualification (IQ)
3. Operational qualification (OQ)
4. Performance qualification (PQ)
Validation: Stages of qualification
Design qualification (DQ)
Design qualification should provide documented
evidence that the design specifications were met
• The process of completing and documenting design
reviews to illustrate that all quality aspects have been
fully considered at the design stage.
• The purpose is to ensure that all the requirements for
the final systems have been clearly defined at the start.
• In other words, has it been designed and selected
correctly
Validation: Stages of qualification
Installation qualification (IQ):
Instillation qualification should provide documented
evidence that the installation was complete and
satisfactory.
•
•
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The purchase specifications.
Drawings.
Manuals.
Spare parts list.
Vendor details.
Should be verified
during installation
qualifications.
Control and measuring devices should be
calibrated.
Validation: Stages of qualification
Operational qualification (OQ):
Operational qualification should provide documented
evidence that utilities, systems or equipment and all its
components operate in accordance to operational
specifications.
In other words, does it work correctly?
•
•
•
•
•
Operation controls.
Alarms.
Switches.
Displays.
Other operational controls.
Should be verified
during operational
qualifications.
Validation: Stages of qualification
Operational qualification (OQ):
Tests should be designed to demonstrate satisfactory operation
over the normal operating range as well as at the limits of its
operation conditions (including the worst conditions).
Measurements made in accordance with a statistical approach
should be fully described.
Validation: Stages of qualification
Performance qualification (PQ)
Performance qualification should provide documented
evidence that utilities, systems or equipment and all its
components can consistently perform in accordance with
the specifications under routine use.
• PQ testing for under trial production.
• Test results should be collected over a
suitable period of time to prove
consistency.
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