PROCESS VALIDATION

2013
DEFINITION

 “Establishing documented evidence which

provides a high degree of assurance that a
specific process consistently produce a
will product meeting its pre-determined
specifications and quality attributes. ’’

(Validation of the individual steps of the

processes is called the
processvalidation.)
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
 Stage
1
– 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.
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.
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.
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.
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
WHEN SHOULD PROCESSES BE VALIDATED?

T h e following m o d e l m a y b e useful in determining wh e th e r or not a p ro ce ss should validated:

A B C
Is P ro c e s s Is Verification Verify &
YES YES
Output Sufficient & Control
Verifiable Co st Effective the P ro c e s s

NO NO

E
D R e d e s i g n P ro d u ct
Validate and/or
P ro c e s s
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

4. low dose/ high potency tablets and capsules
5. drugs with stability problems
6. other tablets and capsules
7. oral liquids, topicals, and diagnostics aids
 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.
 Requirements
 Equipment / facilities meet cGMP
should 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

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.
 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.

 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

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.
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.
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)
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.”
IQ considerations are:

• Equipment features (i.e. material of

construction
design clean ability, etc.)
•Installation conditions (wiring, functionality,
utility, etc.)
•Calibration, maintanance, cleaning
preventative schedules.
• Safety features.
•Supplier prints, drawings and
documentation, manuals.
• Software documented.
• Spare parts list.
•Environmental conditions (such as
cleanroom requirements, temperature, and humidity).
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.
 Following are the contents of equipment
operation qualification:

1. Application S.O.P’s,
2. Utilization List,
3. Process Description,
[Link] Instrument Utilized To Conduct Test,
[Link] Instrument Calibration,
6. Critical Parameters,
7. Test Function (List),
8. Test Function Summaries.
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
 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.
 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.
VALIDATION LIFE CYCLE:
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
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.
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
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.
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 [Link].