Validation......

1. VALIDATION
PRESENTED BY
ONKAR MARKUNDE
DEPATEMENT OF PHARMACEUTICS
KAMLA NEHRU COLLEGE OF PHARMACY,BUTIBORI,NAGPUR

2. ❑ Contents
01) Introduction
02) Need of Validation
03) Scope of Validation
04) Documentation of Validation
=Validation Master Plan
05) Types of Validation
A) Process Validation
B) Cleaning Validation
C) Equipment Validation
D) Validation of Analytical method
06) Validation of specific dosage form
* Solid dosage form

3. Introduction :
* The concept of validation was first proposed by Food and Drug
Administration(FDA) officials, Ted Byers and Bud Loftus, in the mid 1970s in
order to improve the quality of pharmaceuticals.
* Validation is "Establishing documented evidence that provides a high
degree of assurance that a specific process will consistently produce a
product meeting its pre-determined specifications and quality attributes.
* This is to maintain and assure a higher degree of quality of food and drug
products.

4. ❑ Need of validation:
➢Customer satisfaction
➢ Customer mandated
➢ Product liability
➢Control production cost
➢Safety

5. ❑ Scope of validation:
01) Analytical Test Methods
02) Instrument Calibrations
03) Process Utility Services
04) Raw Material
05) Equipment
06) Facilities
07) Product Design
08) Cleaning
09) Operators

6. ❑ Advantages of validation :
01) During the process the knowledge of process increase.
02) Assures the repeatability of the process.
03)Assures the fluency of the production.
04) Assures the product is continuously according to the
marketing authorisation.
05) Decrease the risk of manufacturing problems.
06) Decrease the expense caused by the failures in production
.
07) Decrease the risks of falling in GMP .

7. ❑ Documentation of Validation:
The validation activity cannot be
completed without proper documentation of each and every minute
activity with utmost details. Documentation of validation is generally
different types such as:
01) Validation Master Plan(VMP)
02) Validation Protocol(VP)
03) Validation Reports(VR)
04) Standard Operating Procedure(SOP)

8. ❑ Validation master plans :
A Validation master plan is a document that
summarises the firms overall philosophy, intentions and approach to
be used for establishing performance adequacy.

9. ❑ It includes :
01) Premises
02) Processes
03) Product information
04) Format for protocol and other documentation
05) List of relevant SOPs
06) Planning and scheduling
07) Location
08) Estimation of staffing requirement
09) A time plan of the project

10. ➢ Guidelines on Preparing V.M.P:
01)V.M.P. write on A4 size paper.
02) File in a presentable form.
03) Have sufficient explanatory drawings
04) Clearly divide the V.M.P. in different form.
05) It must be dated and signed properly by authorized persons.
06) If found any step inappropriate is discuss this the F.D.A. people
in advance.

11. ❑ Types of Validation:
The major types of Validation :
01) Process validation
02) Cleaning validation
03) Equipment validation
04) Validation of analytical methods

12. 1) PROCESS VALIDATION:
Definition:
As per FDA Nov.2008,‘The collection of data from the
process design stage throughout production, which establishes scientific
evidence that a process is capable of consistently delivering quality
products.

13. ❑ Types of Process validation:
01) Prospective validation.
02) Retrospective validation.
03) Concurrent validation.
04) Revalidation.

14. ❑ Prospective validation :
* carried out during the development stage by means of 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.

15. ❑ 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 the process.
* The first three production scale batches must be monitored as
comprehensively as possible.
* This careful monitoring of the first three production batches is
sometimes regarded as prospective validation.
* Concurrent validation together with a trend analysis including
stability should be carried out to an appropriate extent throughout the
life of the product.

16. ❑ 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 results of in-process and final control tests are
then evaluated
* Recorded difficulties and failures in production are analyzed to
determine the limits of process parameters.

17. ❑ Revalidation :
* Revalidation is needed to ensure that changes in the
process or in the process environment whether intentional or
unintentional do not adversely affect process characteristics
and product quality.
*Revalidation may be divided into two broad categories:
- Revalidation after any change having being on
product quality
- Periodic revalidation carried out at scheduled intervals

18. ❑ Cleaning validation :
Definition:
“A process of attaining and documenting 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.

19. ❑ Source of contamination:
* Cross contamination product of one product into another.
* Product contamination by a foreign material.
* Microbial contamination.
- Cleaning methods:
* Manual cleaning method.
* Semi automated procedures.
* Fully automated procedures.

20. ❑ Equipment Validation:
Definition:
- As per FDA, May 1987,‘Action of proving that any equipment works
correctly and leads to the expected result is equipment qualification.
- It is not a single step activity but instead result from many discrete
activities.

21. ❑ Steps involved..
01) User requirement specification
02) Design qualification
03) Installation qualifications
04) Operational qualifications
05)Performance qualification

22. Validation of analytical methods :
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 sample.”

23. Specificity :
“The ability to assess unequivocally the analyte in the presence of
components that may be expected to be present, such as impurities
degradation products and matrix components.”
Limit of Quantitation :
“A characteristic of quantitative assays for low levels of compounds in
sample matrices such as impurities in bulk substances and degradation
products in finished pharmaceuticals. It is the lowest amount of analyte in
a sample that can be determined with acceptable precision and accuracy
under the stated experimental conditions.”

24. Range :
“Interval between the upper and lower of analyte (including these levels)
that have been demonstrated to be determined with a suitable level of
precision , accuracy and linearity using the method as written. The range
is normally expressed in the same units as test results. ( e.g. Percentage ,
parts per million, etc.) obtained by the analytical method.”
Ruggedness:
‘’The degree of reproducibility of test results obtained by the analysis of
the same sample under a variety of conditions such as different
laboratories, different analysts, different instruments , different lots of
reagents, different elapsed assay times, different assay temperatures,
different days, etc.”

25. Robustness:
"A measure of its capacity to remain unaffected by small but deliberate
variations in method parameters and provides an indication of its reliability
during normal usage.”
Linearity :
“Its ability to elicit tests that are directly or by a well defined mathematical
transformations proportional to the concentration of analyte in samples
within a given range.”
Limit of Detection :
The lowest amount of analyte in a sample that can be detected but not
necessarily quantitated, under the stated experimental conditions.”

26. ❑ Validation of solid dosage form:
The critical parameters considered during the process validation of
tablet:
01) Mixing and Blending Time
02) Granulation
03) Wet milling
04) Drying
05) Milling
06) Compression
07) Coating