Process validation

1. Process
Validation
Prepared By: Ms. Navdha N. Soni
Assistant Professor
L.J Institute of Pharmacy
Ahmedabad

2. Introduction
• Validation is establishing documented
evidence which provides a high
degree of assurance that a specific
process, procedure or activity carried
out in testing and then production
maintains desired level of compliance
at all stages.
• Validation is a key process for effective
Quality Assurance its simple meaning
is “ACTION OF PROVING”

3. Types of validation
1 Analytical Method
Validation
2
Process Validation
o Prospective Validation
o Concurrent Validation
o Retrospective Validation
o Revalidation
3
Equipment Validation
o DQ
o IQ
o OQ
o PQ
4Cleaning Validation
5 Calibration
6
Raw Material
Validation

4. Process Validation
• It is defined as a documented
programme which provides a high
degree of assurance that a specific
process will consistently produce a
product meeting its predetermined
specification and quality
characteristics.
• Effective process validation contributes
significantly to assuring drug quality.
• The basic principle of quality
assurance is that a drug should be
produced that is fit for its intended
use.

5. • This principle incorporates the
understanding that the following
conditions exist:
1. Quality, safety, and efficacy are
designed or built into the product.
2. Quality cannot be adequately assured
merely by in-process and finished-
product inspection or testing.
• The goal is to create a robust
manufacturing process that
consistently produces a drug
product with minimal variation
that adheres to quality criteria of
purity, identity, and potency.
Process Validation

6. Process Development Stages

7. • The guidelines on general principles of
process validation mentions four types
of validation:
1. Prospective validation (or
premarket validation)
2. Retrospective validation
3. Concurrent validation
4. Revalidation
Types of Process validation

8. Prospective validation
• In Prospective Validation, the
validation protocol is executed before
the process is put into commercial use.
• This approach to validation is normally
undertaken whenever the process for a
new formula (or within a new facility)
must be validated before routine
pharmaceutical production.
• In fact, validation of a process by this
approach often leads to transfer of the
manufacturing process from the
development function to production.

9. • During the product development
phase the production process should
be broken down into individual steps.
• Each step should be evaluated based
on experience or theoretical
considerations to determine the
critical parameters that may affect the
quality of the finished product.
• A series of experiments should be
designed to determine the criticality of
these factors. Each experiment should
be planned and documented fully in
an authorized protocol.
Prospective validation

10. • Using this defined process a series of
batches should be produced and
observations made should be
sufficient to allow the normal extent of
variation and trends to be established
to provide sufficient data for
evaluation.
• Upon completion of the review,
recommendations should be made on
the extent of monitoring and the in-
process controls necessary for routine
production.
Prospective validation

11. • It is generally considered acceptable
that three consecutive batches within
the finally agreed parameters, giving
product of the desired quality would
constitute a proper validation of the
process.
• During this step the input resources
are selected and clearly specified. E.g.
v Material specification is clearly
defined.
v Equipment & process parameter
are defined.
v Operating condition if any
specified.
v Level of training of people can
also be defined
Prospective validation

12. Retrospective Validation
• In many establishments, processes
that are stable and in routine use have
not undergone a formally documented
validation process. Historical data may
be utilized to provide necessary
documentary evidence that the
processes are validated.
• Retrospective validation is only
acceptable for well established detailed
processes that include operational
limits for each critical step of the
process and will be inappropriate
where there have been recent changes
in the formulation of the product,
operating procedures, equipment and
facility

13. • It is generally considered acceptable
that three consecutive batches within
the finally agreed parameters, giving
product of the desired quality would
constitute a proper validation of the
process.
• This approach is rarely been used
today because it’s very unlikely that
any existing product hasn’t been
subjected to the Prospective validation
process.
• It is used only for the audit of a
validated process.
Retrospective Validation

14. • The source of data for retrospective
validation should include amongst
others, batch documents, process
control charts, maintenance logbooks,
finished product test results, and
stability results.
• For the purpose of retrospective
validation studies, it is considered
acceptable that data from a minimum
of ten consecutive batches produced
be utilized.
Retrospective Validation

15. • When less than ten batches are
available, it is considered that the data
are not sufficient to demonstrate
retrospectively that the process is fully
under control.
• In such cases the study should be
supplemented with data generated
with concurrent validation.
Retrospective Validation

16. • Concurrent validation is used for
establishing documented evidence
that a facility and processes do what
they purport to do, based on
information generated during actual
imputation of the process.
• This approach involves monitoring of
critical processing steps and product
testing of current production, to show
that the manufacturing process is in a
state of control
Concurrent Validation

17. • In using this approach there is always
the risk of having to modify process
parameters or specifications over a
period.
• This situation often leads to questions
regarding disposition of the batches
that had already been released for sale,
subsequently known to have undesired
quality characteristics.
Concurrent Validation

18. Revalidation
• Revalidation means repeating the
original validation effort or any part of
it and includes investigative review of
existing performance data.
• This approach is essential to maintain
the validated status of the plant,
equipment, manufacturing processes
and computer systems.
• Re-validation provides the evidence
that changes in a process and /or the
process environment that are
introduced do not adversely affect
process characteristics and product
quality.

19. Revalidation
Revalidation
after any
changes
Periodic
Revalidation

20. Example
• VALIDATION OF WET
GRANULATION PROCESS:
Parameters to be considered during
development & validation are:
BINDER CONCENTRATION &
ADDITION: The optimal binder conc.
will be need to be determined for the
formulation. If the binder solution is
sprayed, it is needed to be diluted
enough so that it can be pumped
through the nozzle. It should also be
sufficiently concentrated to form
granules without over wetting the
materials.

21. Example
AMOUNT OF BINDER SOLUTION:
Too much binder or solvent solution
will over wet the materials and
prolong the drying time.
BINDER SOLUTION ADDITION
RATE: Define the rate at which the
binder solution can be added to the
material.
MIXING RATE: It is the rate required
to ensure the proper formation of
granules. Over mixing of the granules
can lead to harder granules and a lower
dissolution rate.

22. Reference
1. Jain N.K. “Pharmaceutical Product
Development” , CBS Publishers &
Distributors, 2008. Page no. 524-549.
2. Nash R.A. “Pharmaceutical Process
Validation” 3 edition, Marcel & Dekker
publication, Page no. 20-47.
3. Guidance for Pharmaceutical Industry
on Process Validation, USFDA,
January 2011.

23. Questions
Expected Questions
§ Explain Process Validation in detail.