This document provides an overview of validation including: 1. The history and importance of validation in ensuring consistent quality production. Validation became a regulatory requirement after issues with sterility and product quality in the 1960s-1970s. 2. The scope of validation includes facilities, equipment, analytical methods, processes, cleaning, and personnel. 3. Key validation types are prospective, concurrent, retrospective, and revalidation which is required when changes are made. 4. A validation master plan outlines the entire validation program and assigns responsibilities. It provides a comprehensive guide for validation activities.

1. VALIDATION
Prepared by : Masarrat M. Khan.
Designation: Assistant Professor
College: YB. Chavan College of Pharmacy, Aurangabad

2. CONTENTS
• Introduction to Validation
• History of Validation
• Definition of Validation
• Scope of Validation
• Importance of Validation
• Validation of building and facility
• Types of Validation
• Validation Master plan

3. INTRODUCTION TO VALIDATION

4. INTRODUCTION TO VALIDATION
•Validation is the integral part of quality assurance and its simple meaning is
‘action of proving’ (berry, 1988).
•It involves controlling the critical steps of a system, which results in output of
repeatable attributes e.g. a validated tablet manufacturing assures attributes of
product consistently from batch to batch and a validated sterilization cycle assures
the sterility of the product.
•It is neither practical nor feasible to control each and every step of a process,
therefore it is important to identify the number and relative importance of critical
steps of a process that may affect the quality of product and put control on them.
•Validation of a process entails demonstrating that when a process is operated
within specified limits, it will consistently produce product complying with
predetermined requirements.
•Validation of a system indicates that the system has been subject to such a
scrutiny, that results of a system can be practically guaranteed.
•Validation itself does not improve processes but confirms consistent output

5. HISTORY OF VALIDATION

6. HISTORY OF VALIDATION
•Prior to 1978, drug product quality and sterility was based solely on finished
product testing. e.g: sterile products –USP sterility testing
•During this era various incidents took place like Thalidomide tragedy in
1962
•Septicemia outbreaks greatest impact sterility problems with large volume
parentrals (LVP).
•54 deaths and 410 serious injuries
•FDA inspections, products recalls and plant closure.
•USFDA was the pioneer in advocating the concept of process validation
•But till 29th September 1978 the definition of process validation did not
appear in any part of literature of USFDA.
•No cGMP talked about process validation.
• It was only in FDA compliance programme entitled “Drug Process
Inspection” issued in June 1978 ( Before publication of the revised cGMP
Regulations)

7. HISTORY OF VALIDATION
The definition contained was “ A validated
manufacturing process is one, which has been proved to
do what it purports to or is represented to do. The proof
of validation is obtained through the collection and
evaluation of data, preferably, beginning from the
process development phase and continued through in
production phase. Validation necessarily includes
process qualification ( the qualification of materials,
equipment, system, buildings, personnel), but it also
includes the control of the entire process for repeated
batches or runs”.

8. HISTORY OF VALIDATION
•This particular definition did not appear in
any of the yearly revision of that particular
compliance programme. But until march 29,
1983 it was the only official definition of the
process validation.
•On March 29, 1983 draft on guidelines
entiteled “guidelines on General Principles of
process validation” was made available and
same was finalized in May. 1987.

9. DEFINITION OF VALIDATION
The finalized Definition of Validation is
as follows “ A documented programme,
which provides a high degree of
assurance that a specific process will
consistently produce, a product meeting
its pre-determined specification and
quality attributes

10. In which cases we perform validation ?
Validation should be considered in following
situations:
1.Totally new process
2.New equipment
3.Process and equipment, which have been
altered to suit changing priorities.
4.Process where the end test is poor and
unreliable indicator of product quality

11. SCOPE OF VALIDATION

12. SCOPE OF VALIDATION
1. Analytical Tests Methods
2. Instruments Calibration
3. Process utility Services
4. Raw Materials
5. Packaging Materials
6. Equipment
7. Facilities
8. Manufacturing operations
9. Products Design
10.Cleaning
11.Operators

13. IMPORTANCE OF VALIDATION

14. IMPORTANCE OF VALIDATION
Reduction in quality cost
Process optimization
Assurance of quality
Safety

15. REDUCTION OF QUALITY COSTS
Preventive Cost
Appraisal Cost
Internal Failure Cost
External Failure Cost

16. PROCESS OPTIMIZATION
•It means to make the process effective, efficient,
perfect, or useful as possible at the minimum
cost.
•Trained, qualified people are a key element in
any process and thus have the greatest impact on
improving efficiency and productivity

17. QUALITY ASSURANCE
•Validation and process control are at the heart of GMPs.
•Without validated and controlled processes, it is
impossible to produce quality products consistently.
•The end product testing in the absence of validated
processes gives little assure of quality for various reasons
e.g
1. Very limited sample size
2. The limited number of tests performed on a sample
3. Limited sensitivity of the test

18. VALIDTAION OF BUILDING AND FACILLITY

19. VALIDATION OF BUILDING AND FACILITIES
Validation of building and facility may defined as “Obtaining
and documenting evidence to demonstrate that the building and
facility can be relied upon to produce the specified
environmental conditions within pre defined limits”.
Building and facilities should have the following five documents
regarding the validation e.g:
1. User requirement specification (URS)
2. Design Qualification (DQ)
3. Installation Qualification (IQ)
4. Operational Qualification (OQ)
5. Performance Qualification (PQ)

20. U.R.S: U.R.S for building and facilities is a statement spelling out
what the user wants in terms of building and facilities he wants to
create for the manufacture of the pharmaceutical formulation.
Design Qualification: DQ may be considered as the total building
and facility specifications which are approved by the authorized
persons of the client. These specifications are finalized after thorough
discussion with a team of qualified and authorized persons from
production, engineering, project, Quality Management.etc.
Installation Qualification: IQ should refer to the validation of the
empty premises. Validation of the finished, but empty premises will
clearly indicate if the building, facility and the environment is
capable of meeting its predefined specifications.

21. Operational Qualifications: OQ should refer to validation of
equipped but non-operational premises. This is important in order
to determine the air flow pattern in the critical areas associated
with processing equipment, lighting and sound levels should be
carried out.
Performance Qualification: PQ refers to validation of
operational premises. This validation will show us the total
environmental quality with all the influencing factors present.

22. TYPES OF VALIDATION

23. TYPES OF VALIDATION
Prospective validation
Concurrent validation
Revalidation
Retrospective
Validation

24. Laboratory Scale
Pilot Plant Scale up
(3 Batches)
(10 times bigger
than lab scale)
Commercial Scale
(3 Batches)
(10 times bigger
than pilot scale)
PROSPECTIVE VALIDATION
•Prospective validation means which is done on product development stage.
•This validation is carried out in three different stages starting from process
development on laboratory till it reaches to the final commercial level.
•During this stages all the specifications of inputs, parameter limits of the
process and quality specifications including other parameters are finalized and
recorded .
•Each and every step from laboratory to commercial scale is recorded in the
prospective validation document.

25. CONCURRENT VALIDATION
•Concurrent validation is the validation which is carried out during the
production phase.
•After the 3 commercial batches are taken and the process parameter still
goes on
•The parameters are evaluated for the manufacturing facilities batch after
batch and studied if and any change or deviation is required.
•The in process quality control parameters are decided and monitored.
•This becomes the IPCQ tests for regular production, final control and
stability studies.
•Normally 3 batches are recorded fully on a part of initial concurrent
validation program.

26. REVALIDATION
•Revalidation is required under following circumstances:
1. Change in formulae, equipment, procedures or quality of raw materials e.g.
physical variations in raw materials like bulk density, particle size etc.
2. A change in a equipment doing the same process but by different principle will
require revalidation e.g. conventional granulation method and granulation using
rapid mixer granulator or fluid bed processor etc,
3. Replacement of excipient by other excipient in a formulae or a change in
quantity of excipient in formulae.
4. Major changes to process parameters e.g. dry heat sterilization in batch sterilizer
to continuous dry heat sterilization.
5. On appearance of new findings based on current knowledge.
Extent of revalidation depends on the nature and significance of the changes.

27. RETROSPECTIVE VALIDATION
•Retrospective validation may be defined as, “establishing
documented evidence that a system does what it purports to do based
on a review and analysis of historical data and information obtained
during production o clinical or marketable product”
•In some cases retrospective validation is sufficient to establish a
process as valid.
•This validation is allowed when the formulation procedures and
equipment have not been altered.
•A critical examination of the in process control data and of the
analytical results should be performed.
•If existing data is not sufficient, additional tests should be performed.

28. VALIDATION MASTER PLAN

29. VALIDATION MASTER PLAN
•Validation Master Plan is an internally approved
document that describes, in clear and concise wording,
the general expectations, intentions, methods and
approaches to be used during the entire validation effort.
•Size: it should contain at least 400 to 500 pages.
•It should specify clear cut all the activities assign to
various people.
•Legal requirement: The FDA inspectors demand the
validation master plan so as to observe how highly
organized the company validation program is.

30. ADVANTAGES VALIDATION MASTER PLAN
•It provides the complete scope of the activities planned to be
performed in the organization.
•The scope of the activities makes following point clear viz.?
W hat activities are to be performed ?
Who is going to perform these activities ?
When the activities should start and when they should get over?
How the activities will be performed?
What documents will be generated ?
What is the policy on revalidation?
Who are the authorized persons to initiate and review the
validation activities? etc.

31. AREAS COVERED BY VALIDATION MASTER PLAN
•Introduction to the proposed validation program
•Validation of building and facilities
•Validation of equipments used in production and utilities
•Pharmaceutical process validation
•Water system
•HVAC system
•Analytical methods and analytical instrument validation.
•Cleaning validation
•Vendor certification/ RM/PM. Specifications
•Manpower validation

32. ANY QUESTIONS ??