The document discusses validation in the pharmaceutical industry. It defines validation according to WHO, US FDA, and ICH and explains the need, importance, scope and types of validation. The main types discussed are process validation, cleaning validation, equipment validation, and validation of analytical methods. Documentation for validation includes the validation master plan, validation protocols and reports, and standard operating procedures. Qualification is also discussed as being related to but distinct from validation, involving design, installation, operational and performance qualification of equipment.

1. VALIDATION
Mr. Tarif Hussian
M.Pharm. (DRA)
Guided By…..
Dr. (Mrs.) Sanju Nanda
Professor of Pharmaceutics
Presented By…..
Department of Pharmaceutical Sciences
MAHARSHI DAYANAND UNIVERSITY
ROHTAK

2. Contents:-
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 Introduction
 Need of Validation
 Importance of Validation
 Scope of Validation
 Types of Validation
◦ Process Validation
◦ Cleaning Validation
◦ Equipment Validation
◦ Validation of Analytical method
 Documentation
◦ Validation Master Plan
 Qualification
 Relationship between validation and Qualification

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Introduction
WHO Definition:- “The documented act of proving that any procedure, process,
equipment, material, activity of system actually leads to expected result.”
US FDA Definition:- “Process validation is establishing documented evidence which provide
a high degree of assurance that a specified process will consistently produce a product meeting its
pre- determined specifications and quality characteristics.”
ICH Definition:- “Process Validation is the means of ensuring and providing documentary
evidence that processes within their specified design parameters are capable of repeatedly and
reliably producing a finished product of the required quality.”
The concept of validation was first proposed by two FDA officials, Ted Byers and Bud Loftus, in the mid
1970’s in order to improve the quality of pharmaceuticals (Agalloco 1995)

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Need of Pharmaceutical Validation --Validation is an integral part of
quality assurance; It involves the systematic study of systems, facilities and processes aimed
at determining whether they perform their intended functions adequately and consistently as
specified. A validated process is one which has been demonstrated to provide a high degree
of assurance that uniform batches will be produced that meet the required specifications and
has therefore been formally approved. Validation in itself does not improve processes but
confirms that the processes have been properly developed and are under control.
Scope of Validation
Analytical
Facilities
Manufacturing operations
Product Design
Cleaning
Operators
Instrument Calibration
Process Utility services
Raw materials
Packaging materials
Equipment

5. Assurance of quality
Time bound
Process optimization
Reduction of quality cost
Nominal mix-ups, and bottle necks
Minimal batch failures, improved
efficiently and productivity
Reduction in rejection
Increased output
Fewer complaints about process related failures
Reduced testing in process and in finished goods
Avoidance of capital expenditures
Easier scale-up form development work
Easier maintenance of equipment
Improved employee awareness of processes
More rapid automation
Government regulation
Importance of Validation

6. Types of Validation
 Process validation
 Cleaning validation
 Equipment validation
 Validation of analytical method
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 Process Validation:-
♀ The collection and evaluation of data, throughout the product life cycle, which
provides documented scientific evidence that a process is capable of consistently
delivering quality products.
Process validation is a requirement of current Good Manufacturing Practices
(GMPs) for finished pharmaceuticals (21CFR 211) and of the GMP regulations
for medical devices (21 CFR 820) and therefore applies to the manufacture of
both drug products and medical devices.
Types of process validation:-
oProspective validation
oConcurrent validation
oRetrospective validation
oRevalidation
oPeriodic revalidation.

8. Definition – It is an documented
evidence which provide high degree
of assurance that an approved
cleaning procedure will provide
equipment that is suitable for
processing of pharmaceutical
products or API
Importantance:--
 Heart of pharmaceutical activity
 Related to safety and purity of
the products
 Level of cleanliness is achieved by
clean procedure which depends on
its validation.
Cleaning method if performed
confidently, method produced
reproducible results
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Cleaning Validation:--

9. Cleaning Technique
1. Aqueous cleaning
▫ a) Manual cleaning
▫ b) Ultrasonic cleaning
2) Solvent cleaning
a) Extraction
b) Vapour degreasing
c) Ultrasonic cleaning
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LEVEL OF CLEANING:--
LEVEL ATTRIBUTES CLEANING VALIDATION
LEVEL-0
Batch to batch cleaning
in an identical process
(same intermediate and
same API). Change in the
early stage of another
process
Not required
LEVEL-1
Changes in early
steps to intermediate
of another product (
API to intermediate )
Required but not necessary
LEVEL-2
Changeover from one
API to another API.
Changeover any
intermediate to any
API. Changeover from
early step to final step
of same product
Essential

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ELEMENTS OF CLEANING VALIDATION
 Establishment of acceptance criteria
 Product , equipment , facilities to be clean
 Cleaning agents
 Cleaning procedure
 Cleaning mechanism
 Sampling Analytical methods
 Establishment of limits
 Documentation Validation report

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Cleaning Validation Process -
♠ It mainly include 4 stages
Stage 1 :-
Determine the most appropriate cleaning procedure for the
equipment
Develop and validate the sampling and chosen analytical
method for the compound being cleaned
Evaluate equipment surface and determine

13. Stage 2 :-
Develop a cleaning validation protocol for the product and equipment
being cleaned.
Stage 3 :-
Generate interim(time) cleaning validation report on a clean by clean basis.
Stage 4 :-
Generate a cleaning validation report detailing the acceptability of cleaning
procedure for the product and equipment .
CONCLUSION Of Cleaning Validation:-- Clean environment and clean
operations is the heart of pharmaceutical activities. Four basic requirements of
cGMP are safety, identity, strength and purity which can be achieved by cleaning
process and its proper validation.

14. Validation of Equipments 14
The basic component of pharma industry are the ‘Equipments’. Therefore
before validating a process that is carried out in a pharma industry, the issue of
equipment validation becomes a prime importance. Equipment validation is
covered in several steps:
 User requirement specifications/ customer requirements(USR)
 Design Qualification(DQ)
 Installation Qualification(IQ)
 Operational Qualification(OQ)
 Performance Qualification(PQ)
Principle:- Equipment must be located ,designed, constructed,
adapted, maintained to suit the operations to be carried out.

15. to minimize risks of error.
to permit effective cleaning and maintenance.
To avoid:
1. cross-contamination, dust and dirt build-up.
2. any adverse effect on the quality of products.
Equipment must be installed to:
1.minimize risks of error.
2.minimize risks of contamination.
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Equipment layout and design must aim:

16. What is Documentation?
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“ Documentation is any communicable material that is used to
describe, explain or instruct regarding some attributes of an
object, system or procedure, such as its parts, assembly,
installation, maintenance and use.”
Documentation provides Both;
1. Information on when, where, who, why & How to
Complete tasks
2. Evidence providing that the tasks have been completed
as they should be.

17. Types of document used :
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MPs (Make Parameters ) Training schedules
Change Control documents Calibration form
Temperature & humidity Chart SOPs (Standard Operating
Procedure)
CAPA (Corrective Action
Preventive Action)
Daily Plans
DPRs (Detailed Project Reports) Emergency repair & maintenance form

18. 1. Validation Master Plan (VMP)
2. Validation protocols (VP)
3. Validation reports(VR)
4. Standard Operating Procedures (SOPs)
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Types of Documentation

19. PICS-Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme
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Validation Master Plan (VMP) :
# A Validation Master Plan (VMP) is a comprehensive
document describing the applicable validation
requirements for the facility, and providing a plan for
meeting those requirements.
As per PICS:
A Validation Master Plan is a document that
summarizes the firm's overall philosophy, intentions and
approach to be used for establishing performance
adequacy.

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SCOPE OF (VMP) :
Minimize noncompliance costs
Reduce rework
Reduce rejected lots
 Avoid recalled lots
 Helps in new drug approval
 Satisfactory inspections
 Corporate image
 Financial gain
Secure third-party contracts
 Corporate legal protection

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 It sets the overall goals and limits.
Referred thought the project.
To understand the scope of the validation and so avoid misconceptions.
 To define the scope of the project.
Why to Perform VMP?:
VMP is not a requirement of FDA ,but it has become almost
an industry standard
IMPORTANCE:

22. Contents of VMP :
* Introduction
* Methodology
* Qualification:DQ,IQ,OQ,PQ
* Personnel
* Schedule
* Preventative maintenance
* Change control
* Procedure
* Documentation
* Appendices
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Which factors are considered in VMP?:

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Qualification is part of validation, but the individual qualification steps
alone do not constitute process validation.
Qualification of instruments is not a single, continuous process but instead results
from many discrete activities. For convenience, these activities have been
grouped into 4 phases of qualification.
 Design Qualification (DQ)
 Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
QUALIFICATION
“It is the action of proving and documenting that equipment or ancillary
systems are properly installed, work correctly, and actually lead to the
expected results.”

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Design qualification - Documented verification that the proposed design
of facilities, systems and equipment is suitable for the intended purpose.
Installation Qualification- Documented verification that the installations
(such as machines, computer system components, measuring devices, utilities
and manufacturing areas) used in a processor system are appropriately
selected and correctly installed in accordance with established specifications.
Operational Qualification- Documented verification that the system or
subsystem operates as intended over all anticipated operating ranges.
Performance Qualification- Documented verification that the equipment
or system performs consistently and reproducibly within defined specifications
and parameters in its normal operating environment.

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Re – Qualification:
Modification to, or relocation of equipment should follow satisfactory review
and authorization of the documented change proposal through the change
control procedure. This formal review should include consideration of re-
qualification of the equipment.
RELATIONSHIP BETWEEN VALIDATION AND
QUALIFICATION
Qualification and Validation are essentially the same. The term
qualification is normally used for equipment and utilities, and
validation for systems and processes. In this sense, qualification
can be seen as part of validation. Where the term “validation” is
used in the document, the same principles may be applicable for
“qualification’’

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VERIFICATION IS
A PERFECT
PROOF OF A
THEORY
Swami
Vivekananda

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