Introduction of validation & ICH guidelines & WHO guidelines for validation & equipment validation types of validation.

1. ITM UNIVERSITY GWALIOR
ASSIGNMENT ON - VALIDATION
PRESENTED BY - MINEETA MAHRA
M. PHARMA. ( 1ST SEM. )

2. TABLE OF CONTENTS
 INTRODUCTION
 SCOPE
 MERITS
 TYPES OF VALIDATION
 VALIDATION MASTER PLAN
 VALIDATION OF SPECIFIC DOSAGE FORM
 VALIDATION OF EQUIPMENT
 ICH & WHO GUIDELINES FOR VALIDATION
OF EQUIPMENT
 ICH & WHO GUIDELINES FOR CALIBRATIO
N OF EQUIPMENT
 REFERENCE

3. INTRODUCTION
Validation is the documented act of proving that any proc
edure , process , equipment , material , activity or system
actually leads to the expected result
ISO Defination
Validation is the confirmation by examination and the provisi
on of objective evidence that the particular requirements for a
specific intended use are fulfilled .
According to the Food and Drug Administration (
FDA), the goal of validation is to:

4. "establish documented evidence which provides a high de
gree of assurance that a specific process will consistently p
roduce a product meeting its predetermined specifications
and quality attributes."
PURPOSES OF VALIDATION
 To accept an individual sample as a member of a po
pulation under study.
 To admit samples to the measurement process.
 To minimize later questions on sample authenticity.
 To provide an opportunity for resampling when nee
ded.

5. SCOPE OF VALIDATION
• Validation requires an appropriate and sufficient infrastr
ucture including:
- organization, documentation, personnel and finances In
• volvement of management and quality assurance personn
el.
• Personnel with appropriate qualifications and experience.
• Extensive preparation and planning before validation is p
erformed.
• A specific programme for validation activities in place.
• Validation done in a structured way according to docume
ntation including procedures and protocols.
• Process, materials and equipment to prove consistent yiel
d of a product of the required quality.
• Manufacturers to identify what validation work is needed
.

6.  for new premises, equipment, utilities and systems an
d processes and procedures;
 at periodic intervals;
 and when major changes have been made.
• Validation should be performed
• Validation in accordance with written protocols.
• A written report on the outcome to be produced.
• Validation over a period of time,
 e.g. at least three consecutive batches (full production
scale) to demonstrate consistency. (Worst case situatio
ns should be considered.).
 Demonstrate suitability for new manufacturing formul
a or method.
• Significant changes (facilities, equipment, processes) sho
uld be validated

7. MERITS OF VALIDATION
• During the process the knowledge of process increases.
• Assures the repeatability of the process.
• Assures the fluency of production.
• Assures that the product is continuously according to the
marketing authorisation.
• Decreases the risk of the manufacturing problems.
• Decreases the expenses caused by the failures in producti
on.
• Decreases the risks of failing in GMP.
• Decreases the expenses of the every day production even
though the validation itself will create expenses.

8. TYPE OF VALIDATION
The major type of validation:
 Process validation
 Cleaning validation
 Equipment validation
 Validation of analytical methods

9.  Process of validation
As per FDA Nov.2008, The collection of data from the proces
s design stage throughout production,which establishes scienti
fic evidence that a process is capable of consistently deliverin
g quality products.
Type of process validation
• Prospective validation
• Retrospective validation
• Concurrent validation
• Revalidation

10. • Prospective validatio
n
 carried out during the development stage by means of a ris
k analysis of the production process, which is broken down
into individual steps.
 These are then evaluated on the basis of past experience to
determine whether they might lead to critical situations.
 Where possible critical situations are identified, the risk is
evaluated, the potential causes are investigated and assesse
d for probability and extent, the trial plans are drawn up, a
nd the priorities set.

11. • Retrospective validation
 Retrospective validation involves the examination of past ex
perience of production on the assumption that composition,
procedures, and equipment remain unchanged
 such experience and the results of in-process and final contr
ol tests are then evaluated.
 Recorded difficulties and failures in production are analyzed
to determine the limits of process parameters.

12. • Concurrent validation
 carried out during normal production.
 This method is effective only if the development stage has
resulted in a proper understanding of the fundamentals of th
e process.
 The first three production-scale batches must be monitored
as comprehensively as possible.
 The nature and specifications of subsequent in-process and
final tests are based on the evaluation of the results of such
monitoring.
 This careful monitoring of the first three production batche
s is sometimes regarded as prospective validation.
 Concurrent validation together with a trend analysis includi
ng stability should be carried out to an appropriate extent th
roughout the life of the product.

13. • Revalidation
• Revalidation is needed to ensure that changes in the process
and/or in the process environment, whether intentional or un
intentional, do not adversely affect process characteristics an
d product quality.
• Revalidation may be divided into two broad categories:
 Revalidation after any change having a bearing on pr
oduct quality.
 Periodic revalidation carried out at scheduled interva
ls.

14.  Cleaning validation
"A process of attaining and document in sufficient evidence to g
ive reasonable assurance, given the current state of Science and
Technology, that the cleaning process under consideration does,
and / or will do, what it purpoes to do."
Objective
 To minimize cross contamination.
 To determine efficiency of cleaning process.
 To do troubleshooting in case problem identified in the cle
aning process and give suggestions to improve the process

15.  Equipment validation
• As per FDA, May 1987,'Action of proving that works cor
rectly and leads to the expected result is equipment qualif
ication.
• any equipment It is not a single step activity but instead r
esult from many activities.

16.  Validation of analytical methods
• "The process by, which it is established, by laboratory stu
dies, that the performance characteristics of the method m
eet the requirements for the intended analytical applicatio
n"
Accuracy
"The closeness of test results obtained by that method to the tr
ue value. This accuracy should be established across its range.
"
Precision
"The degree of agreement among individual test results when
the method is applied repeatedly to multiple sampling of a ho
mogenous sample."

17. VALIDATION MASTER PLAN ( VMP )
 A Validation Master Plan is a document that summarises th
e firm's overall philosophy, intentions and approach to be us
ed for establishing performance adequacy.
 The validation master plan could consist of :
• Approval page and table of contents.
• Introduction and objectives.
• Facility and process description.
• Personnel, planning and scheduling.
• Responsibilities of committee members.
• Process control aspects.
• Equipment, apparatus, processes and systems to be valid
ated.
• Acceptance criteria .

18. • Documentation e.g. validation protocols and reports.
• SOPS.
• Training requirements.
It also have the following contents :
a. Introduction to validation policy, scope, location and schedule.
b. Organizational structure with response to personnel and respon
sibilities.
c. Plant / process /production description mentioning rationale for
inclusion or exclusion, extend of validation.
d. Specific process considerations that are critical & require extra
attention.
e. List of products/processes/systems to be validated summarised
in a matrix format , validation approach.
f. Revalidation activities, actual status and future planning.
g. Key acceptance criteria H.
h. Documentation format I.
i. Reference to required SOPS

19. VALIDATION OF SPECIFIC DOSAGE FO
RM
 The objective of the design and manufacture of the solid dosa
ge form(tablet,capsule) is to deliver orally the correct amount
of drug in the proper form,over a period of time and in the des
ired location and to have its chemical integrity protected to th
at point.
 The prime objective of any pharmaceutical plant is to manufa
cture product of high quality consistently at the lowest possibl
e cost.
 Through a careful design & validation of both the process an
d controls , the manufacturer can establish a high degree of co
nfidence that all manufactured units from successive lots will
be acceptable.

20.  The product quality can be ensured by,
① Chemical and physical stability 1. 2.
② Preservation against microbial contamination
③ Uniformity of dose of drug
④ Acceptability to users (prescriber & patient)
⑤ Suitable packaging & labelling 3. 4. 5. 6.
⑥ Validation.
 Tablets as a dosage form comprises a mixture of active subst
ances and excipients, usually in powder form ,pressed (or) c
ompacted in to solid
 The excipients include:
• Binder , glidants & lubricants - to ensure efficient tabl
etting
• Disintegrant – to promote tablet break up in the GIT
• Sweetner/flavour- to enhance taste
• Pigment – to make the tablet visually attractive

21.  Polymer coating is often applied to make the tablet :-
• Smoother.
• Easy to swallow.
• Control the release rate of active ingredients.
• More resistant to environment.
• Extending its shelf life.
• To enhance appearance of the tablet.
 The manufacturing of tablet includes extensive powder hand
ling
 The powder must blended for uniformity and converted in to
the dosage form through compression.
 The typical requirement include ,
• Weight
• Blending
• Mixing/granulation areas
• Compression
• Coating

22. VALIDATION OF EQUIPMENT
 Validation is the establishment of documentary evidence wh
ich provide a high degree assurance of specified process wil
l consistently produce the product meeting with predetermin
ed specification and quality attributes.
 Validation studies are performed for analytical equipment, t
ests, facility systems such as air, water, steam, the manufact
uring, cleaning, sterilization processes
 Validation of equipment includes the qualification of the e
quipment which entails Design Qualification - DQ, Install
ation Qualification - IQ, Operational Qualification - OQ a
nd Performance Qualification - PQ. Validation also includ
es training, SOPS on operation, cleaning, maintenance, ca
libration, etc.

24. ICH GUIDELINES FOR CALIBRATION
OF EQUIPMENT
• Local identification by a unique identification number and
involvement in the master GMP instrument list.
• Procedure for instrument history file.
• Aproval by quality unit.
• Generation of procedure for verification and standardisatio
n of accuracy and reliability.
• For approval of procedure, it must contains steps and form
s required for calibration.
• Involvement of calibration stickers and auxiliary stickers p
rogram.
• Procedure for tracking of scheduled calibration activities.
• Procedure for notifying users of calibration due dates, over
due calibrations and out of tolerance findings.

25. WHO GUIDELINES FOR CALIBRATION
OF EQUIPMENT
• Regular calibration.
• Establishment of specific procedure of calibration for every
equipment.
• Only authorized personnel should operate equipment.
• Availability of up to date instructions for calibration.
• Verification results must be recorded on a control chart.
• Unique identification of each item of equipment for calibrat
ion.
• Keeping of records of each item of equipment to perform c
alibration.
• Systematic verification of laboratory to prevent contaminati
on.
• Establishment of maintenance procedure. Out of service eq
uipment. Labelling of equipment.

26. ICH GUIDELINES FOR VALIDATION O
F EQUIPMENTS
• meter distance from walls and other obstacles.
• Easy to operate, clean and maintainable.
• Working should be at proper commissioned position.
• Certification of equipment.
• Checking of overhead heights.
• Proper source of light.
• Drop down utility system.
• Design of equipment.
• Layout of equipment.
• Marking of pipelines as per their flow of direction.
• Sop the equipment.
• Tracing of equipment.
• Identification marking for equipment.
• Cleaning of equipment.Tracing.

27. WHO GUIDELINES FOR VALIDATION
OF EQUIPMENTS
• Equipment must be located, designed, constructed, adapted a
nd maintained to suit the operation.
• Layout and design of equipment.
• Instalment of equipment.
• Production equipment.
• Labelling of fixed pipe work.
• Cleaning of equipment.
• Labelling of equipment.
• Establishment of written procedures for each operation.
• Record keeping.

28. REFERENCE
1. Potdar Manohar A. "Pharmaceutical quality assurance" 2n
d Edition, Nirali Prakashan, p-8.1-8.7.
2. P. P. Sharma, "Validation in Pharmaceutical Industry- con
cepts, approaches & guidelines", 1* edition, 2007 Vandan
a Publication House.quality.
3. . B. T. Loftus & R. A. Nash, "Pharmaceutical Process Vali
dation", Drugs and Pharm Sci. Series, Vol. 129, 3rd Ed.,
Marcel Dekker Inc., N.Y.elines.
4. Guidelines : ICH. "ICH harmonization for better health".
Available from: http://www.ich.org/products/ guidelines.ht
ml.