Process validation

1. Process Validation

2. What is Process Validation?
Process Validation is defined as the collection
and evaluation of data, from the process
design stage throughout production, which
establishes scientific evidence that a process is
capable of consistently delivering quality
products

3. Definition
 Validation master Plan (VMP):
The validation master plan is a high level document that
establishes an umbrella validation plan for the entire project
and summarizes the manufacturers overall philosophy and
approach.
Qualification:
Documented evidence that premises, systems or equipments
are able to achieve the predefined specifications properly
installed, and/or work correctly and lead to the expected
results.
Validation:
Actions of proving and documenting that any process,
procedure or method actually and consistently lead to the
expected results.

4. Validation Master Plan (VMP)
1. Qualification and Validation
2. Planning for Validation
3. Documentation
4. Qualification
5. Process Validation
6. Cleaning Validation
7. Change Control
8. Revalidation

5. Elements Of Validation
Qualification is pre-requisite of validation. The qualification includes
the following:
1. Design Qualification (DQ):-
Mechanical drawings and design features provided by the
manufacturer of the equipment should be examined.
2. Installation Qualification (IQ):-
Installation qualification should be carried out on new or modified
facilities, systems and equipment. The following main points
should be includes in the installation qualification.
 Checking of installation of equipment, piping, services and
instrumentation.
 Collection of supplier’s operating working instructions and
maintenance requirements and their calibration requirements.
 Verification of materials of construction
 Sources of spares and maintenance

6. 3. Operational Qualification (OQ):-
Operational qualification should include the following:
 Tests developed from the knowledge of the processes systems
and equipment
 Defining lower and upper operating limits,. Sometimes, these
are called ‘worst case’ conditions.
4. Performance Qualification (PQ):-
PQ should include the following:
 Tests using production materials, substitutes or simulated
product. These can be developed from the knowledge of the
process and facilities, systems or equipment.
 Tests to include conditions with upper and lower limits

7. Steps involved in the process validation

8. Types of Process Validation
 Prospective Validation: Prospective validation is performed in
a research and development lab on a small scale.
 Retrospective Validation: Retrospective validation is
performed after the dispatch of product in the market.
 Concurrent Validation: Concurrent validation is performed in
the production area after getting satisfying results of
prospective validation.
 Revalidation: This validation is conducted Whenever there are
changes in packaging, formulation, equipment or processes
which could have impact on product effectiveness or product
characteristics, there should be revalidation of the validated
process.

9. Prospective Validation
 Prospective validation is establishing
documented evidence that a system
performs as it is intended based on pre-
planned protocol.(Before process
implementation).
 Prospective validation is performed in a
research and development lab on a
small scale.

10. When To Perform
 Developing new products.
 Any change in the manufacturing process which
has a major effect on the product quality.
 before starting the routine batches of
production.
 stage of product development.

11. What to Do
 carried out in the research and development stage so its start from
developing formulation.
 Formulation of a new product is developed at this stage.
 Specification of raw materials are defined.
 Procedure for manufacturing is developed in the form of validation
protocol.
 Procedure for cleaning validation is defined.
 All the critical points are observed on risk based analysis.
 Process parameters like mixing time, drying time etc are defined and
adjusted to get desired results.
 Batch Manufacturing Record is prepared.
 Testing method for analyzing the product is developed.
 Sampling plan is prepared.
 Technology transfer documents are prepared.
 Environmental factors like temperature and humidity and storage
conditions are defined.

12. Results
 Usually three batches are manufactured at this stage
and all should produce desired results using the same
parameters.
 If we have to make changes in parameters of the first
batch to adjust the results, these changes are made
through proper change control procedure.
 The batch in which we make changes will not be
considered the validation batch.
 We will have to take the next three batches with the
same parameters to build confidence that our
procedures and methods are reliable.

13. Retrospective Validation
 Retrospective validation is documented evidence
that products manufactured in the pharmaceutical
industry using validated procedure maintain its
quality and purity in the market during the period
of its shelf life.
 Retrospective validation is performed after the
dispatch of product in the market.

14. What to Do?
 In the pharmaceutical industries the reference samples are withdrawn from
the finish product batches before its dispatch to the market.
 After the specified time period the sample is taken from the reference samples
and is tested.
 It is done to ensure that our product in the market is still meeting a quality
attribute during its shelf life.
 Following type of data is also collected during Retrospective validation,
 Number of batches manufactured for a defined period of time.
 Batch size
 Strength of the product.
 Manufacturing and expiry date of the product.
 Master documentation.
 List of deviations and corrective actions.
 Stability testing data for different batches.
 It is used for audits of validated processes.

15. Concurrent Validation
 The word concurrent can be remembered by a simple
word current, which means this type of validation is
performed on current production batches.
 Concurrent validation is performed in the production
area after getting satisfying results of prospective
validation.
 In concurrent validation the product is manufactured
in the production area using the production facility
and equipment.

16. When to Perform
 Product which has completed its prospective stage, is
validated in the production area during concurrent
validation.
 When there is a change in process which has no significant
effect on product quality.
 Change in a raw material source.
 Technical Transfer
 When there is change in equipment used.
 When there is only change in tablet strength and previous
strength was validated by the prospective validation and
change strength has the same ratio of API and Excipients.

17. What to Do?
 Before starting the concurrent validation it is ensured that
the operators involved in the manufacturing process are
trained.
 All the equipment, utility and systems are qualified.
 Three batches are manufactured to ensure the same
product quality.
 In concurrent validation all the critical parameters of
batches which are under manufacturing are observed.
 All the parameters are adjusted according to prospective
validation.
 Sampling plan is followed as provided by the product
development department.

18. Summery
 In concurrent validation we manufacture the
large scale batches using the same parameters
as manufactured in small scale during
prospective validation to ensure that our
process developed is capable of producing the
quality results.
 Samples are checked at specified time
intervals.
 Prospective validation is done for three
batches.

19. Re-Validation
 Validation is done once in the product life
cycle until there is no change in the product
manufacturing parameters.
 In some specific circumstances we have to
revalidate our products.

20. When To Re-validate
 change in critical parameters.
 change in product formulation.
 change in the product process.
 change in equipment.
 change in the facility.
 change in primary packaging.
 change in raw material density, particle size etc.
 Source change of API.
 Change in any process parameter like mixing time, drying temperature,
etc
 change in batch size.
 change in the plant.(Shifting from one plant to other)
 Periodically checking the validation results.
 When the product fails to meet the specification.