types of validation

1. MODERN PHARMACEUTICS
Presented by-
ABDUL NAIM
M – Pharm – Pharmaceutics
1-st semester

2. Validation:- validation is confirmation by examination and the
provision of objective evidence that the particular
requirements for a specific intended use are fulfilled
TYPES OF VALIDATION
THE MAJOR TYPES OF VALIDATION
1. Process validation
2. Cleaning validation
3. Equipment validation (Qualification )
4. Validation of analytical method

3. Process validation
Definition
• As per FDA Nov,2008, ‘the collection of data from the process design
state throughout production, which establishes scientific evidence
that a process is capable of consistently delivering quality products.
Types of process validation:
Prospective validation
Retrospective validation
Concurrent validation
Revalidation

4. a. Prospective validation
• Carried out during the development stage by means of a risk 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.

5. b. Concurrent validation
Concurrent validation is validation which is carried out during normal
production.
It is appropriate when:-
• it is more appropriate to validate process during routine production
due to well understanding of process.
• Extensive testing and monitoring ensure the desired quality
characteristics of product with high degree of confidence

6. C. Retrospective validation
• Retrospective validation involves the examination of past experience
of production on the assumption that composition, procedures, and
equipment remain unchanged
• Such experience and the results of in-process and the final control
tests are then evaluated
• Recorded difficulties and failure in production are analysis to
determine the limit of process parameters

7. d. Revalidation
• Revalidation is needed to ensure that changes in the process and/or
in the process environment, do not adversely affect process
characteristics and product quality.
• Revalidation may be divided into two broad categories:
 Revalidation after any change having a bearing on product quality.
 Periodic revalidation carried out at scheduled intervals.

8. 2. Cleaning validation
Definition
“A process of attaining and document in sufficient evidence to give
reasonable assurance, given the current state of science and
technology, that the cleaning process under consideration does, and/or
will do, what it purpose to do.”
Objective..
• To minimize cross contamination.
• To determine efficiency of cleaning process
• To do troubleshooting in case problem identified in the cleaning
process and give suggestions to improve the process

9. 3. Equipment validation
Definition :-
• As per FDA, May 1987, ‘Action of proving of providing that any
equipment works correctly and leads to the expected results is
equipment qualification.
• It is not single step activity but instead result from many activities.

10. 4. Validation of analytical method
Definition:-
• “the process by, which it is established, by laboratory studies, that the
performance characteristics of the method meet the requirements for
the intended analytical application.”
Accuracy :
“The closeness of test results obtained by that method to the true
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 homogenous

11. VALIDATION OF SOLID DOSAGE FORMS
• The objective of the design and manufacture of the solid dosage
form(tablet, capsule) is to deliver orally by correct amount of drug in
the proper from, over a period of time and in the desired location and
to have its chemical integrity protected to that point.
• The prime objective of any pharmaceutical plant is to manufacture
product of high quality consistently at the lowest possible cost.
• Through a careful design & validation of both the process and
controls, the manufacturer can establish a high degree of confidence
that all manufactured units from successive lots will be acceptable.

12. • The product quality can be ensured by,
1. Chemical and physical stability
2. Preservation against microbial contamination
3. Uniformity of dose of drug
4. Acceptability to users(prescriber & patient)
5. Suitable packaging and labelling
6. Validation
• Tablets as a dosage form comprises a mixture of active substances and
excipients, usually in powder form, pressed (or) compact in to solid
• The excipients include
1. Binder, glidants and lubricant- to ensure efficient tabletting
2. Disintegrant - to promote tablet break up in the GIT

13. 3. Sweetener/flavour – to enhance taste
4. Pigment – to make the tablet visually attractive
• Polymer coating is often applied to make the tablet :-
1. Smoother
2. Easy to swallow
3. Control the release rate of active ingredients
4. More resistant to environment
5. Extending its shelf life
6. To enhance appearance of the tablet

14. • The manufacturing of tablet includes extensive powder handling
• The powder must blended for uniformity and converted in to the
dosage from through compression.
• The typical requirement include
1. Weight
2. Blending
3. Mixing/ granulation areas
4. Compression
5. Coating

15. GOVERNMENT REGULATION
• This emphasis on validation began in the late 1970 s, the requirement
has been set at 1963 as cGMP for finished pharmaceuticals.
• There shall be return procedures for production and process control
designed to assure that the drug products have the identity strength,
quality, purity.
• Validation is considered to be integral part of GMPs essentially
worldwide, compliances with validation requirements is necessary for
obtaining approval to manufacture and to introduce new products.
• The FDA’s cGMP refer to the concepts of the validation in both
sections.

16. • They state that such control procedure shall be established to
monitor output and to validate the performance of those
manufacturing process that may be responsible for causing variability
in the characteristics of in process materials and drug materials.
• The accuracy, sensitivity, specificity and reproducibility of test
methods employed by the firm shall be established and documented.
• A generally stated requirement for process validation is contained in
the medicinal device GMP regulations.
• Where deviations from device specification could occur as result of
manufacturing process itself.
• There shall be written procedures describing any process controls
necessary to assure conformance to specifications.

17. Manufacturing process model

18. Facilities
Facilities for URS(user requirement specification):-
• User requirement specifications may be define as the ,user
department will raise the indent for his requirement regarding
machine ,equipment or software. He will give his requirement in a
one format is called the URS which including the functional and
technical specification for the machine ,equipment or software ,these
specification written is called the URS.

19. General format for URS :
• Name of organization (URS )
• Date ….
• Name of your department …….
• Location …….
• Name of machine , or software ……
• Purpose of machine ….
• software……….
• Other area impact …..(AHU space )

20. • SL.NO Parameter Specification
• 1 Name
• 2 Model
• 3 Make
• 4 Capacity
• 5 Calibration
• 6 Spare
• 7 Change part 8 others

21. • Facilities For Design qualification-(DQ)
• Once the URS is finalized the Engineering department, R&D ,user, QA
department will prepare the design qualification ,which including
drawing ,calculation ,sample & other design document .¨
Manufacturer will study the design ,if the design is ok from the
construction point of view manufacturer will quote to the user . if the
design is not ok from the construction ,national & international point
of view. machine manufacture will prepare new drawing from the
construction as well as legal & user point of view .than these drawing
is send to user for approval.

22. 1 -General
2 -Document approval
3 -Version control
4 -Abbreviation
5 -Objective
6 -Responsibility
7 -URS 8 Equipment
9- DQ review and approval ,etc.

23. • Facilities Of Installation qualification (IQ)
•Installation qualification is the documented
verification that the system is installed
satisfactory & is compliance with other
appropriate engineering code, manufacturing
and approval specification and that instrument is
calibrated & all service are available & of
adequate .

24. • IQ protocol
• ¨ Validation file
• ¨ Security access
• ¨ Environment
• ¨ System diagnostics
• ¨ hardware component
• ¨ Instrument installation & calibration
• ¨ Electric power & circuit protection
• ¨ Instrument air supply
• ¨ Loop wiring

25. • ¨ Hardware configuration
• ¨ Software backup and restoration
• ¨ General system inspection
Facilities Of Operational qualification(OQ):
The computer must be power backup & check to ensure it functioning
correctly .This may be involve observing & recording system status lamp
& rerunning diagnostic check

26. OQ protocol
• Operator interface & screen display
• ¨ Input/ output signal
• ¨ Data storage ,backup & restore
• ¨ Electrical record &electrical signature
• ¨ System report printout
• ¨ Trend display
• ¨ Alarm event & massages

27. • ¨ Safety interlocks
• ¨ Control & Monitoring loop wiring
• ¨ Software process logic
• ¨ SOP preparation & approval
• ¨ Power failure & data recovery

28. Performance qualification(PQ)
Performance qualification is an documented verification that
computerized operation consistently perform as intended in the URS
throughout all the anticipated operating range . Performance
qualification are a collection of test cases used to verify that a system
perform as expected under simulated real world Condition The
performance and equipment for its routine analytical use is check to
ensure that complies with its specification .