An Approach to Process Validation 

Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

DEPARTMENT OF PHARMACY,               

 
KATHMANDU UNIVERSITY, DHULIKHEL, 
KAVRE, NEPAL

   
A
AnnA
Appp
prrooa
acch
h ttoo,,

PROCESS VALIDATION

SUBMITTED BY: BIBEK SINGH MAHAT

M. PHARM. 1ST YEAR, 1ST SEM. ROLL NO: 07

Submitted to:
JAYABIR KARMACHARYA
Department of Pharmacy
Kathmandu University
Kavre, Nepal
(0 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

 
 

AN APPROACH TO,
PROCESS VALIDATION
 
SUBMITTED FOR INTERNAL EVALUATION FOR
THE DEGREE IN MASTER IN PHARMACY
BY
BIBEK SINGH MAHAT, M. PHARM STUDENT,
1ST YEAR, 1ST SEMESTER, BATCH OF 2009

SUBMITTED TO:

JAYABIR KARMACHARYA
DEPARTMENT OF PHARMACY
SCHOOL OF SCIENCE
KATHMANDU UNIVERSITY
DHULIKHEL, NEPAL

(1 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

TABLE OF CONTENTS:
 

1. VALIDATION……………………………………………………………………3

2. PROTOCOLS……………………………………………………………………5

3. MASTER VALIDATION PLAN……………………………………………..5

4. QUALIFICATIONS…………………………………………………………….6

5. PLANNING FOR VALIDATION……………………………………………8

6. PROCESS VALIDATION……………………………………………………..9

6.1. Prospective validation…………………………………………….11

6.2. Concurrent validation…………………………………………….12

6.3. Retrospective validation…………………………………………13

6.4. Revalidation…………………………………………………………14

6.5. Laboratory- and pilot-scale validations……………………...14

7. Typical content requirements for process validations……………15

8. REFERENCES…………………………………………………………………16

Attachment: Annex 1: FORMAT OF PROCESS VALIDATION PROTOCOL

(2 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

1. VALIDATION
“Validation is a key element of the quality assurance system in a pharmaceutical company”

For a long time, our understanding of pharmaceutical quality was such that one relied solely on
the control of raw materials and final products. The intermediate process was guaranteed by
established experience and the professional honesty of longtime employees. Today, our
understanding is almost the reverse. Well-tested raw materials from qualified suppliers are used
in a process that must be so well controlled that, theoretically, absolutely nothing can result other
than a product that conforms to the specifications. In contrast, the place of manufacture and staff
carrying out production are interchangeable, as long as they are qualified.

The new approach is conclusive, reasonable, sensible, since if a serious defect is identified at the
final product quality control, irreparable damage has already occurred. For drug products,
reprocessing is prohibited in most cases or is only possible with a great deal of additional
expenditure. Since modern drug substances and innovative preparations are also becoming ever
more expensive, it is, therefore, necessary to avoid the final product being rejected using
preventive measures, such as validation. Therefore, to guarantee a reproducible quality,
processes must be validated. 4

Definitions:-
ƒ “The establishing of documented evidence which provides a high degree of assurance that a
planned process will consistently perform according to the intended specified outcomes”.
(WHO guide to GMP requirements , part-2 ,validation, Geneva 1997)
ƒ "Action of proving, in accordance with the principles of Good Manufacturing Practice, that
any procedure, process, equipment, material, activity or system actually leads to the expected
results.” (EU GMP Guideline)

ƒ “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.”(U. S. Food and Drug Administration)

Validation is an essential part of good manufacturing practices (GMP). It is, therefore, an

element of the quality assurance program associated with a particular product or process. The
basic principles of quality assurance have as their goal the production of products that are fit for
their intended use. These principles are as follows: - 3

a) Quality, safety and efficacy must be designed and built into the product.
b) Quality cannot be inspected or tested into the product.
c) Each critical step of the manufacturing process must be validated. Other steps in the
process must be under control to maximize the probability that the finished product
consistently and predictably meets all quality and design specifications.

(3 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

Validation of processes and systems is fundamental to achieving these goals. It is by design and
validation that a manufacturer can establish confidence that the manufactured products will
consistently meet their product specifications. Documentation associated with validation
includes3:-

a) Standard operating procedures (SOPs)

b) Specifications
c) Validation master plan (VMP)
d) Qualification protocols and reports
e) Validation protocols and reports.

The implementation of validation work requires considerable resources such as3:

a) Time: generally validation work is subject to rigorous time schedules.
b) Financial: validation often requires the time of specialized personnel and expensive
technology.
c) Human: validation requires the collaboration of experts from various disciplines (a
multidisciplinary team, comprising quality assurance, engineering, manufacturing and other
disciplines, depending on the product and process to be validated).

Validation studies verify the system under test under the extremes expected during the process to
prove that the system remains in control. Once the system or process has been validated, it is
expected that it remains in control, provided no changes are made. In the event that
modifications are made, or problems occur, or equipment is replaced or relocated, revalidation is
performed. Critical equipment and processes are routinely revalidated at appropriate intervals to
demonstrate that the process remains in control. The validity of systems / equipment / tests/
processes can be established by prospective, concurrent or retrospective studies. 1

For pharmaceutical manufacturers, validation should be understood not as a discretionary rule,

but as a mandatory requirement that must be complied with. Thus validation is addressed
regularly in regulatory inspections as well as in supplier audits and there are still numerous
deficiencies observed: about 10 % of all GMP complaints are in the context of validation - at
fourth place in the ranking for all GMP complaints. 5

Common deficiencies include: 5

ƒ Validation protocols have not been compiled or are not being followed
ƒ Information about the equipment used, the critical process parameters, sampling data,
number of validation batches or acceptance criteria is missing from the validation
documentation
ƒ Changes to validated processes are not being addressed

(4 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

2. PROTOCOLS
A protocol is a written set of instructions broader in scope than a Standard Operating Procedure
(SOP). SOPs are the detailed written instructions for procedures routinely performed in the
course of any of the activities associated with pharmaceutical manufacturing.

A protocol describes the details of a comprehensive planned study to investigate the consistent
operation of new system / equipment, a new procedure, or the acceptability of a new process
before it is implemented. Protocols include significant background information, explain the
rationale for and the objective of the study, give a full description of the procedures to be
followed, set out the parameters to be measured, describe how the results will be analyzed, and
provide pre-determined acceptance criteria for making conclusions. 1

Validation studies, stability studies, and clinical studies are examples of written protocols for
pharmaceutical manufacturers. Validation protocols are important in ensuring that documented
evidence is taken which demonstrates that an equipment item, a system, a process or a method
consistently performs at a specified level.

3. MASTER VALIDATION PLAN

The Master Validation Plan (also written as : Validation Master Plan ,VMP) is a document
pertaining to the whole facility that describes which equipment, systems, methods and processes
will be validated and when they will be validated. The document should provide the format
required for each particular validation document (Installation Qualification, Operational
Qualification and Performance Qualification for equipment and systems; Process Validation;
Analytical Assay Validation), and indicate what information is to be contained within each
document. 1

The Master Validation Plan should also indicate why and when revalidations will be performed,
either after changes or relocation of equipment or systems; changes to processes or equipment
used for processing; or for changes in assay methods or in equipment used in tests. 1

If a new process or system is implemented, a Design Qualification (DQ) may be necessary.

Guidelines for such cases should be included in the Master Validation Plan. A Design
Qualification would be necessary when planning and choosing equipment or systems to ensure
that components selected will have adequate capacity to function for the intended purpose, and
will adequately serve the operations or functions of another piece of equipment or operation.

The order in which each part of the facility is validated must be addressed in the Master
Validation Plan. For example the water system should be validated before validating a piece of
equipment that uses this water system.

The DQ, IQ, OQ and PQ must be performed in order: the master validation plan should indicate
how to deal with any deviations from these qualifications, and state the time interval permitted
between each validation. 1

(5 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

4. QUALIFICATIONS
i) Design qualification (DQ)

The first element of the validation of new facilities, systems or equipment could be design
qualification (DQ).The compliance of the design with GMP should be demonstrated and
documented.

ii) Installation qualification (IQ)

This document should be written for the critical processing equipment and systems that are used
within the facility, e.g. an HVAC system, an autoclave or a pH meter. The IQ should list all the
identification information, the location, utility requirements and any safety features of the
equipment.
The IQ protocol prepared for each piece of equipment or system lists the name, description,
model and identification numbers, the location, utility requirements, connections, and any safety
features of the system/equipment which needs to be documented.
It should verify that the item matches the purchase specifications, and that all drawings, manuals,
spare parts list, vendor address and contact number, and other pertinent documentation are
available. 1

Installation qualification (IQ) should be performed on new or modified facilities, systems and
equipment. IQ should include, but not be limited to the following:- 2

a) Installation of equipment, piping, services and instrumentation checked to current

engineering drawings and specifications;
b) Collection and collation of supplier operating and working instructions and maintenance
requirements;
c) Calibration requirements;
d) Verification of materials of construction.

iii) Operational qualification (OQ):-

This document outlines the information required to provide evidence that all the components of a
system or of a piece of equipment operate as specified. This involves testing of all normal
operation controls; all alarm points, all switches and displays, interacting controls, and any other
indications of operations and functions. The OQ document should provide a listing of SOPs (or
reference to specific manual instructions) for operation, maintenance and calibration;
information on the training of operators; and instructions for any static or dynamic tests to show
that the equipment operates as expected under normal conditions. Specifications and acceptance
criteria must be defined for all the operations. The OQ document should include information on
equipment or system calibration, pre-operational activities, routine operations and their
acceptance criteria. 1

(6 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

Operational qualification (OQ) should follow Installation qualification. OQ should include, but
not be limited to the following: 2

a) Tests that have been developed from knowledge of processes, systems and equipment;
b) Tests to include a condition or a set of conditions encompassing upper and lower operating
limits, sometimes referred to as “worst case” conditions.
c) The completion of a successful Operational qualification should allow the finalization of
calibration, operating and cleaning procedures, operator training and preventative
maintenance requirements. It should permit a formal "release" of the facilities, systems and
equipment.

iv) Performance qualification (PQ):-

This part of the validation for systems and equipment is performed after both Installation and
Operational Qualifications have been completed, reviewed and approved. The PQ document
describes the procedure or procedures for demonstrating that a system or piece of equipment can
consistently perform and meet required specifications under routine operation and, where
appropriate, under worst case situations.

The PQ should include a description of the preliminary procedures required, the detailed
performance test(s) to be done, and the acceptance criteria for each test. The PQ also requires
that other supporting equipment used during the qualification have been validated. 1

Performance qualification (PQ) should follow successful completion of Installation qualification

and Operational qualification.
PQ should include, but not be limited to the following: 2
a. Tests, using production materials, qualified substitutes or simulated products that have been
developed from knowledge of the process and the facilities, systems or equipment;
b. Tests to include a condition or set of conditions encompassing upper and lower operating
limits.
Although PQ is described as a separate activity, it may in some cases be appropriate to perform it
in conjunction with OQ.

v) Qualification of established (in-use) facilities, systems and equipment:- 2

Evidence should be available to support and verify the operating parameters and limits for the
critical variables of the operating equipment. Additionally, the calibration, cleaning, preventative
maintenance, operating procedures and operator training procedures and records should be
documented.

(7 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

5. PLANNING FOR VALIDATION

i) VALIDATION MASTER PLAN:- 2
All validation activities should be planned. The key elements of a validation program should be
clearly defined and documented in a validation master plan (VMP) or equivalent documents. The
VMP should be a summary document which is brief, concise and clear. The VMP should contain
data on at least the following:-
a) Validation policy;
b) Organizational structure of validation activities;
c) Summary of facilities, systems, equipment and processes to be validated;
d) Documentation format: the format to be used for protocols and reports;
e) Planning and scheduling;
f) Change control;
g) Reference to existing documents.

ii) DOCUMENTATION:- 2
a) A written protocol should be established that specifies how qualification and validation will
be conducted.
b) The protocol should be reviewed and approved.
c) The protocol should specify critical steps and acceptance criteria.
d) A report that cross-references the qualification and/or validation protocol should be
prepared, summarizing the results obtained, commenting on any deviations observed, and
drawing the necessary conclusions, including recommending changes necessary to correct
deficiencies.
e) Any changes to the plan as defined in the protocol should be documented with appropriate
justification.
f) After completion of a satisfactory qualification, a formal release for the next step in
qualification and validation should be made as a written authorization.

iii) CHANGE CONTROL:- 1

A qualification/validation study is designed for defined parameters and measures specified
outcomes. Any modifications made to equipment, systems, processes or procedures may change
the parameters or affect the expected outcomes. Therefore any change that is made after initial
validation is complete must be controlled. The following are the factors to be considered during
change control:-

a) The effect of the change on the specific system /process under consideration as well as the
wider implication for other systems and processes of the facility.
b) Re-validation of the system/process or other systems may be necessary depending on the
significance of the change.
c) No changes should be made for any validated, approved equipment /systems /tests /
processes without formal review and approval via the change control procedure.

(8 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

6. PROCESS VALIDATION
Process validation is a fundamental component of the quality assurance system of
pharmaceutical manufacturers. It should verify that the procedures and processes used in drug
product manufacturing are appropriate to their purposes and guarantee that the manufactured
drug product is of the required quality. Process validation is, thus, a basic factor for drug product
safety. 5

A process is a series of interrelated functions and activities using a variety of specified actions
and equipment which is designed to produce a defined result. To validate the reproducibility and
consistency of a process, the full defined process is carried out using validated equipment, under
the established procedure usually at least 3 times The process must successfully and consistently
meet all acceptance criteria each time to be considered a validated process. In many cases, "worst
case" conditions are used for the validation to ensure that the process is acceptable in the extreme
case. Sometimes worst case conditions for systems can only really be tested over time and hence
must be evaluated using a rigorous long term monitoring program. 1

Examples of processes which must be validated in pharmaceutical manufacturing are: 1

1. Cleaning
2. Sanitization
3. Fumigation
4. De-pyrogenation
5. Sterilization
6. Sterile filling
7. Fermentation
8. Bulk production
9. Purification
10. Filling, capping, sealing

Each of these categories may apply to several distinct processes in the manufacturing facility.
For instance, cleaning process can be the cleaning of glassware, the cleaning of the facility
(floors and walls), equipment cleaning such as Clean-in-Place (CIP), or Clean-out-of-Place
(COP), cleaning of garments, etc. Sterilization can be the Sterilize-in-Place (SIP) process,
glassware sterilization, filter sterilization, steam sterilization, dry heat sterilization, etc.

Each process to be validated must be a specific process clearly described in a Master Formula or
in an SOP. All the equipment, the processing parameters, and the specifications at each step must
be detailed. Complete descriptions of the identity, code numbers, construction, operating
capacity, and actual operating ranges must be defined for the equipment. The processing
parameters for all steps must be sufficiently detailed to permit complete reproducibility of the
process each time it is performed: time periods, pH, volumes, temperatures, measurements,
specifications, acceptable ranges, etc. The controls and tests and their specifications must be
defined. The purity profiles for production processes must be defined for each step. To be
considered validated, the process must consistently meet all specifications at all steps throughout
the procedure at least three times consecutively. 1

(9 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

It is very important that the specifications for a process undergoing validation be pre-determined.
It is also important that for all critical processing parameters for which specifications have been
set, there must be equipment to measure all of those parameters during the validation study.

Process Validation studies examine a process under normal operating conditions to prove that the
process is in control. Once the process has been validated, it is expected that it remains in
control, provided no changes are made. In the event that modifications to the process are made,
or problems occur, or equipment or systems involved in the process are changed, a re-validation
of the process would be required. 1

Very often validation studies require that more measurements are made than are required for the
routine process. The validation must prove the consistency of the process and therefore must
assess the efficiency and effectiveness of each step to produce its intended outcome. 1

General Considerations:-

a) Process validation should normally be completed prior to the distribution and sale of the
medicinal product (prospective validation). In exceptional circumstances, where this is not
possible, it may be necessary to validate processes during routine production (concurrent
validation). Processes in use for some time should also be validated (retrospective
validation).

b) Facilities, systems and equipment to be used should have been qualified and analytical
testing methods should be validated. Staff taking part in the validation work should have
been appropriately trained.

c) Facilities, systems, equipment and processes should be periodically evaluated to verify that
they are still operating in a valid manner.

(10 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

6.1. Prospective validation

If a new drug product or new manufacturing procedure is planned to be submitted for marketing
authorization, it must be validated. In these cases, validation activities must be performed
prospectively. By this, it is understood that proof is established that a manufacturing procedure
using the process parameters established on the basis of findings from process development, up-
scaling/pilot plant leads reliably to a product with the desired or labeled quality on the
production scale.

Definition: - A prospective validation is a validation conducted prior to distribution of either a

new product, or product made under a revised manufacturing process, where the revisions may
affect the product quality. A prospective validation should be carried out with at least three
consecutive batches. The three batches must comply with the specifications. 5

1) Prospective validation should include, but not be limited to the following:- 2

a. Short description of the process;

b. Summary of the critical processing steps to be investigated;
c. List of the equipment/facilities to be used (including measuring/ monitoring/
recording equipment) together with its calibration status finished product
specifications for release;
d. List of analytical methods, as appropriate;
e. Proposed in-process controls with acceptance criteria;
f. Additional testing to be carried out, with acceptance criteria and analytical validation,
as appropriate;
g. Sampling plan;
h. Methods for recording and evaluating results
i. Functions and responsibilities;
j. Proposed time-table.

2) Using this defined process (including specified components) a series of batches of the final
product may be produced under routine conditions. In theory the number of process runs
carried out and observations made should be sufficient to allow the normal extent of variation
and trends to be established and to provide sufficient data for evaluation. It is generally
considered acceptable that three consecutive batches/runs within the finally agreed
parameters would constitute a validation of the process. 2

3) Batches made for process validation should be the same size as the intended industrial scale
batches. 2

4) If it is intended that validation batches be sold or supplied, the conditions under which they
are produced should comply fully with the requirements of Good Manufacturing Practice,
including the satisfactory outcome of the validation exercise, and with the marketing
authorization. 2

(11 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

6.2. Concurrent validation

The "Inspection of qualification and validation in pharmaceutical manufacture and quality

control" aide mémoire points out that concurrent validation should only be used in exceptional
cases that must be justified. The same requirements as for prospective validation apply for
carrying out and documenting concurrent validation. Here too, a minimum of 3 validation
batches must be evaluated. 5

Considerations are as follows: - 2

a) In exceptional circumstances it may be acceptable not to complete a validation program

before routine production starts.
b) The decision to carry out concurrent validation must be justified, documented and approved
by authorized personnel.
c) Documentation requirements for concurrent validation are the same as specified for
prospective validation.

Examples for application of the "concurrent validation" approach: - 5

a) Transfer of a validated process to another manufacturing site, e.g. to a contract manufacturer

b) Supplementation of missing data within a retrospective validation
c) Long time interval between the manufacture of consecutive batches
d) Periodic revalidation
e) Validation of small changes to already validated processes that are well controlled (e.g. new
dosage or different tablet shape)
f) Validation of variations in batch sizes (up-scaling or downscaling)

(12 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

6.3. Retrospective validation

During retrospective validation, the reliability of the manufacturing process is assessed and
documented on the basis of historical data which was collected in connection with batches that
have already been manufactured.
Definition: - “A retrospective validation is the validation of the manufacturing procedure for a
product already in distribution based upon available production, in-process control and quality
control data. A retrospective validation should be carried out with no fewer than ten batches and
must, generally, be supplemented with prospective cycles".5

Considerations of Retrospective Validation:- 2

a) Retrospective validation is only acceptable for well-established processes and will be

inappropriate where there have been recent changes in the composition of the product,
operating procedures or equipment.
b) Validation of such processes should be based on historical data. The steps involved require
the preparation of a specific protocol and the reporting of the results of the data review,
leading to a conclusion and a recommendation.
c) The source of data for this validation should include, but not be limited to batch processing
and packaging records, process control charts, maintenance log books, records of personnel
changes, process capability studies, finished product data, including trend cards and storage
stability results.
d) Batches selected for retrospective validation should be representative of all batches made
during the review period, including any batches that failed to meet specifications, and
should be sufficient in number to demonstrate process consistency. Additional testing of
retained samples may be needed to obtain the necessary amount or type of data to
retrospectively validate the process.

Requirements for a retrospective validation: - 5

a) Compilation of a validation protocol with risk analysis, definition of critical parameters,
establishing of acceptance criteria
b) The facilities and equipment used must be qualified and the measuring points calibrated
c) Traceability of sampling (intervals, sample sizes, etc.) for IPC and quality control
d) Homogeneity of historical records (i.e. all batches considered are manufactured and tested
in accordance with the same authorized manufacturing and test procedure. In case of
changes have been made to product composition, instructions or equipment, the exact
timing must be traceable.
e) Analysis of at least 10 consecutive batches - from the statistical point of view and from the
point of view of FDA inspectors, only 20 batches are even acceptable.
f) Data from 10 -20 batches of the product produced using the same stable manufacturing
process should be analyzed, to demonstrate that the manufacturing process is under control
and `capable’.
g) A Cpk (Process Capability) of 1.0, 1.33 and 2.0 represents a 3, 4, 6 sigma respectively. The
measurement of Cp or Cpk will be accepted as one of the statistical methods for analyzing
the process control.

(13 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

6.4. REVALIDATION:-
Facilities, systems, equipment and processes, including cleaning, should be periodically
evaluated to confirm that they remain valid. Where no significant changes have been made to the
validated status, a review with evidence that facilities, systems, equipment and processes meet
the prescribed requirements fulfils the need for revalidation.1

6.5. Laboratory- and pilot-scale validations:-1

The validation of some production processes cannot always be carried out in the production
facility. One example of this is the validation of removal of impurities by individual purification
steps in the process. It is not acceptable to bring high levels of unacceptable impurities
(endotoxins, DNA, unwanted proteins, contaminating bacteria and viruses) to spike into the
process to demonstrate their removal or inactivation by the purification process. Such validation
studies are performed in laboratories at a smaller scale designed to approximate the full scale
process.

Pilot-scale* is an intermediate scale which is sometimes used to determine the validity of new or
modified processes before full-scale operations are attempted. For both lab-scale and pilot scale
validation studies to be acceptable as proof of the validity of the full scale process, it must be
demonstrated that the scale-down has been calculated for all critical parameters of the process:
times, temperatures, amounts, column sizes, flow rates, pressures, etc.

*Pilot Scale Batches:

These may be used in the development or optimization stage. Pilot batch size should correspond
to at least 10% of the future industrial-scale batch. For oral solid dosage forms this size should be
at least 10% or 100,000 units whichever is greater unless otherwise justified. 4

(14 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

7. Typical content requirements for process validations:-1

It is vital that during all process validation studies, the processes are performed in the "actual"
environment under which production is to occur. That is to say all routine peripheral activities
associated with this process must be in effect while the validation is being performed. (e.g.
number of personnel in facility, exit and entry procedures are in effect, environmental and
personnel monitoring is being performed on the prescribed schedule, air system is operating as
for regular manufacturing,

CONTENT OF PROCESS VALIDATION SCHEME:-4

Validation studies to be conducted on the production scale batches. It should contain the
following information:-

a) A short description of the manufacturing process in a schematic drawing or flow chart

b) A summary of the critical processes, control variables and justification for their selection
c) Finished product specification (release)
d) Details analytical methods (reference to the dossier)
e) In process controls proposed with acceptance criteria
f) Additional testing intended to be carried out (e.g. With proposed acceptance criteria and
analytical validation appropriate)
g) Sampling plan – where, when and how samples are taken
h) Details of methods for recording and evaluation of results
i) Proposed time frames for carrying out the studies
j) Content of Validation
k) Report : The following information should be provided in the report:

i. Summary
ii. Introduction
iii. Batches used for validation
iv. Manufacturing equipment
v. Critical process steps and parameters
vi. Acceptance criteria
vii. Sampling plan
viii. Tabulation of the test results
ix. Batch Analysis
x. Evaluation of data, and where applicable, including statistical process control
analysis
xi. Evaluation of data including comparison against acceptance criteria
xii. Discussion on deviations and out of specification results
xiii. Conclusion and recommendations

1, 2, 3
REFER ANNEX -1:- FORMAT OF PROCESS VALIDATION PROTOCOL

(15 of 16) 
 
 An Approach to Process Validation 
Bibek Singh Mahat, M. Pharmacy, 1st Year, 1st Sem. Roll No. 7 

8. REFERENCES:-

1. A WHO guide to good manufacturing practice (GMP) requirements Part 2: Validation.

Written by: Gillian Chaloner-Larsson, Ph.D, GCL Bioconsult, Ottawa Roger Anderson,
Ph.D, Director of Quality Operations, Massachusetts Public Health Biologic Labs Anik
Egan, BSc., GCL Bioconsult, Ottawa ( WHO/VSQ/97.02 ; World Health Organization
Geneva 1997).

2. EUROPEAN COMMISSION, Pharmaceuticals and cosmetics, Working Party on Control of

Medicines and Inspections; Final Version of Annex 15 to the EU Guide to Good
Manufacturing Practice; Title: Qualification and validation, Brussels, July 2001.

3. Quality assurance of Pharmaceuticals, A compendium of guidelines and related materials

Volume 2, 2nd updated edition Good manufacturing practices and inspection, World Health
Organization 2007

4. ASEAN GUIDELINES ON PROCESS VALIDATION

5. GMP Manual , Good Manufacturing Practice and Implementation, Anita Mass, Barbara
Peither , Thomas Peither , Mass and Peither GMP Publication, Germany , 2006

(16 of 16)