2. DEFINITION
“Establishing documented evidence which
provides a high degree of assurance that a
specific process will consistently produce a
product meeting its pre-determined
specifications and quality attributes. ’’
(Validation of the individual steps of the
processes is called the processvalidation.)
3. Process validation involves a series of activities taking
place over the lifecycle of the product and process.
This guidance describes process validation activities in
three stages.
Stage 1 – Process Design
Stage 2 – Process Qualification
Stage 3 – Continued Process Verification
4. – Process Design : During this stage the commercial
manufacturing process is defined based on knowledge
gained through development and scale-up activities.
Stage 2
– Process Qualification: During this stage, the process
design is evaluated to determine if the process is capable
of reproducible commercial manufacturing.
Stage 3
– Continued Process Verification: Ongoing assurance is
gained during routine production that the process remains
in a state of control.
Stage1
5. A successful validation program depends upon information
and knowledge from product and process development.
So that manufacturers should.
Understand the sources of variation
Detect the presence and degree of variation
Understand the impact of variation on the process and
ultimately on product attributes.
Control the variation in a manner commensurate with the
risk it represents to the process and product.
6. GENERAL CONSIDERATIONS FOR PROCESS VALIDATION
An integrated team approach to process validation that
includes expertise from a variety of disciplines. Project
plans, along with the full support of senior management,
are essential elements for success.
All studies should be planned and conducted according
to sound scientific principles, appropriately documented,
and approved in accordance with the established
procedure
Homogeneity within a batch and consistency between
batches are should be the goals of process validation
activities.
7. Objectives
To establish a record keeping system that considers all
concept of manufacturing process which includes controlled
testing.
To evaluate all possible sources of variation in process.
To identify all sources of variation those are possible from
the materials, machines, methods and men.
To evaluate the requirement for in-process testing and
evaluation.
To document everything that is done to follow establish
procedures and protocols as closely as possible.
Quality, safety and effectiveness must be designed and built
in to the product.
Quality must be assured.
8. WHEN IS VALIDATION NEEDED?
Before introduction of a new method into routine use
Whenever the conditions change for which a method
has been validated, e.g., instrument with different
characteristics
Whenever the method is changed, and the change is
outside the original scope of the method
9. WHEN SHOULD PROCESSES BE VALIDATED?
A
Is Process
Output
Verifiable
B
Is Verification
Sufficient &
Cost Effective
C
Verify &
Control
the Process
D
Validate
E
Redesign Product
and/or
Process
YES YES
NO NO
The following model may be useful in determining whether or not a process should validated:
10. PROCESS VALIDATION: ORDER OF PRIORITY
A) Sterile product and their processes
1. large volume parenterals
2. Small volume parenterals
3. Ophthalmics, other sterile products, and medical devices
B) Non sterile products and their processes
1. low dose/ high potency tablets and capsules
2. drugs with stability problems
3. other tablets and capsules
4. oral liquids, topicals, and diagnostics aids
11. TYPES OF PROCESS VALIDATION
Prospective ProcessValidation
an experimental plan called the validation protocols executed
before the process is put into commercial use.
Most validation efforts require some degree of prospective
experimentation to generate validation support data.
Its is normally carried out in connection with the introduction
of new drug products and their manufacturing processes.
12. Requirements
Equipment / facilities should meet cGMP
requirements.
Personnel have an awakeness about the
requirements.
Critical processing stages and process variables are
identified.
At least one qualification trial (size x 100) made which
shows that there is no significant deviation from
expected performance of process.
Batches should be run at different days, shifts and
different quantities.
13. Retrospective Process Validation
It is chosen for established products whose
manufacturing processes are considered stable and
when on the basis of economic considerations alone and
resource limitations, prospective validation programs
cannot be justified.
Wherein the numerical in-process and/or end-product
test data of historic production batches are subjected to
statistical analysis.
The equipment, facilities and subsystemsused in
connection with the manufacturing process must be
qualified in conformance with CGMP requirements.
14. Requirements
Gather all historical data of process/ product in
chronological sequence according to batch manufactured.
Data should consists of atleast last 20-30 manufactured
batches for analysis.
Trim data by eliminating results of non-critical steps.
Subject the resultant data to statistical analysis and
evaluation.
Draw the control charting & go for conclusion.
15. Advantages
No additional samples necessory, only need history data.
No additional testing required.
Cost saving compared with prospective.
No additional risk.
No longer time need.
Trained persons are easily available to perform the work.
It can be adopted to various types of processes/ products.
Well suited for existing product which are not validated
previously.
16. Concurrent Process Validation
It is in-process monitoring of critical processing steps and
end-product testing of current production.
It can provide documented evidence to show that the
manufacturing process is in a state of control.
It provides validation documentation from the test
parameter and data sources disclosed in the section on
retrospective validation.
17. Process Re-Validation:
Required when there is a change in
any of the critical process parameters,
formulation,
primary packaging components,
raw material ,
major equipment or premises.
Failure to meet product and process specifications in
batches would also require process re-validation.
18. BASIC PRNCIPLE FOR PROCESS VALIDATION
the individual qualification steps alone do not
constitute process validation.
1. Installation Qualification (IQ)
2. Operational Qualification (OQ)
3. Performance Qualification (PQ)
19. 1. Installation Qualification (IQ)
“Installation qualification establishes that the instrument is
received as designed and specified, that it is properly
installed in the selected environment, and that this
environment is suitable for the operation and use of the
instrument.”
20. IQ considerations are:
• Equipment design features (i.e. material of
construction clean ability, etc.)
• Installation conditions (wiring, utility, functionality,
etc.)
• Calibration, preventative maintanance, cleaning
schedules.
• Safety features.
• Supplier documentation, prints, drawings and
manuals.
• Software documented.
• Spare parts list.
• Environmental conditions (such as cleanroom
requirements, temperature, and humidity).
21. Operational Qualification (OQ):
"Operational qualification (OQ) is the process of
demonstrating that an instrument will function according to
its operaational specification in the selected environment.”
The proper operation of equipment is verified by
performing the test functions specified in the protocol.
A conclusion is drawn regarding the operation of
equipment after the test functions are checked and all
data has been analyzed.
22. Following are the contents of equipment
operation qualification:
1. Application S.O.P’s,
2. Utilization List,
3. Process Description,
4.Test Instrument Utilized To Conduct Test,
5.Test Instrument Calibration,
6. Critical Parameters,
7. Test Function (List),
8. Test Function Summaries.
23. Performance Qualification (PQ):
"Performance Qualification (PQ) is the process of
demonstrating that an instrument consistently performs
according to aspecification appropriate for its routine
use ".
PQ should always be performed under conditions
that are similar to routine sample analysis.
PQ should be performed on a daily basis or
whenever the equipment is being used.
In practice, PQ can mean system suitability testing,
where critical key system performance characteristics
are measured and compared with documented.
24. PQ considerations include:
• Actual product and process parameters
andprocedures established in OQ.
• Acceptability of the product.
• Assurance of process capability as established in
OQ.
• Process repeatability, long term process stability.
25. VALIDATION TEAM
Personnel qualified by training and experience in a
relevant discipline may conduct such studies.
The working party would usually include the following
staff members such as;
Head of quality assurance.
Head of engineering.
Validation manager.
Production manager.
Specialist validation discipline: all areas.
27. VALIDATION PROTOCOL
The validation protocol should contain the following
elements,
Short description of the process.
Summary of critical processing steps to be
investigated.
In process, finished product specification for release.
Sampling plans.
Departmental responsibility.
Proposed timetable.
Approval of protocol
28. THE VALIDATION REPORT
The report should include at least the following
Title and objective of study.
Reference to protocol.
Details of material.
Equipment.
Programes and cycles used.
Details of procedures and test methods.
Result.
Recommendations on the limit and criteria to be
applied on future basis.
29. IMPORTANCE OF PROCESS VALIDATION
Improve the use of technology
Improve the business benefits
Improve operational efficiency
Improve compliance with regulations
Reduce the risk of failure
Reduce the cost
Process optimization
Increased customer satisfaction
30. CONCLUSION:
Validation is one of the important steps in achieving
and maintaining the quality of the final product. If
each step of production process is validated we can
assure that the final product isof the best quality.
Finally it can be concluded that process validation is
a key element in the quality assurance of
pharmaceutical product as the end product testing is
not sufficient to assure the quality of finished
product.
31. References:
Sharma sumeet, Singh gurpreet. process validation in
pharmaceutical industry: an overview . J Drug De &
Therap; 2013, 3(4),184-88.
Fraderick J. Carleton, James P. Agalloco ; validation of
pharmaceutical processes; 2nd edition ,1999 New York ;
page No.257-59.
Berry IR, Nash RA. Pharmaceutical process validation.
2nd ed. 1993 Newyork: Marcel Dekker.Inc.
Notas do Editor
(e.g., process engineering, industrial pharmacy, analytical chemistry, manufacturing, and quality assurance).
