Types of Validation
Submitted to: submitted by:
Dr. GAURAV K JAIN NASR ALI
Pharmaceutics Dep. 1St semester M.pharm.
JAMIA HAMDARD JAMIA HAMDARD
THE MAJOR TYPES OF VALIDATION :
Process validation .
Validation of analytical methods .
Process validation :
Process validation is the means of ensuring and providing documentary
evidence that processes are capable of repeatedly and reliably
producing a finished product of the required quality.
pre-requisites for process validation:
qualification of manufacturing equipment and instruments as well as the
formulation ,this involve compatibility of active ingredients and
recipients and of final product and packaging materials.
Critical services (water, air, nitrogen, power supply).
Equipment cleaning and motivation of personnel.
TYPES OF PROCESS VALIDATION :
(a) PROSPECTIVE VALIDATION.
(b) CONCURRENT VALIDATION.
(c) RETROSPECTIVE VALIDATION.
(d) PROCESS RE-VALIDATION.
A- Prospective validation:
is 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
Expected that process validation be completed prior to the
release of the finished product for sale. 5
● Initial stages of formulation development and process development
● Setting of process sampling plans.
● Designing of batch records.
● Defining raw material specifications.
● Transfer of technology from scale up to commercial size batches.
● Environmental controls.
It is generally considered acceptable that three consecutive
batches within the finally accepted parameters, that assure
product of the desired quality would constitute a proper validation
of the process.
B- Concurrent validation:
is used on the batches currently being produced for establishing
documented evidence that a facility and process do what they claim to
Examples of these may be when:-
A previous validated process is being transferred to a third party
contract manufacturer or to another site.
The number of batches produced are limited.
Process with low production volume per batch and market demand.
The product is a different strength of a previously validated product
with the same ratio of active or inactive ingredients. 7
C- 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 final
control tests are then evaluated. Recorded difficulties and failures
in production are analyzed to determine the limits of process
Retrospective validation is obviously not a quality assurance measure
in itself, and should never be applied to new processes or products.
means repeating the original validation effort or any part of it.
Process re-validation is required when there is a change in any of the
critical process parameters ,formulation, primary packaging components,
major equipment or premises.
for examples when:-
Changes in raw materials:
( physical properties such as density, viscosity, particle size distribution or
changes in source of active raw material manufacturer) 9
Changes in packaging material ( primary container/ closure system).
Changes in the process (Mixing time, drying temperatures & batch
Changes in the equipment.
Changes in the plant/facility.
Cleaning validation :
Cleaning validation ensures that there is no cross contamination in a
multi-product manufacturing plant and also prevents microbial
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.
Source of contamination:
Cross contamination product of one product into another.
Product contamination by a foreign material.
Factors Influencing Cleaning validation :
Product, Equipment, Facilities, Cleaning methods, Cleaning agents,
Sampling, Testing, Limits, and acceptance criteria.
Equipment validation is to provide a high level of documented evidence
that the equipment and the process confirm to a standard.
DESIGN QUALIFICATION .
OPERATIONAL QUALIFICATION .
Validation of analytical methods:
Method validation must prove that the analytical method used for a
specific test is suitable for which it is to be carried out.
Methods should be validated :-
When they are to be established for routine use.
When the method is to be changed due to change in conditions.
Whenever the equivalence between new method and the standard are
TYPES OF PROCEDURES TO BE VALIDATED:
The accuracy of an analytical method refers to the closeness of agreement
between the observed value and the value which is either conventially a
true one or reference one.
The precision of an analytical method refers to the closeness of values
obtained from a series of tests.
Repeatability is established when the same sample is estimated repeatedly
by the same analyst using same analytical method within the same
laboratory using same instrument and performed within a short period of
4) INTERMEDIATE PRECISION:- When the test is repeated on different days
by different persons or using different instruments within the same
laboratory, the variation is expressed in terms of intermediate precision.
5) REPRODUCIBILITY:- When a method is standardized, the test is carried
out in different laboratories using the same method, the precision
between the laboratories is referred to as reproducibility.
6) SPECIFICITY:- Specificity is the ability of a test method to measure the
analyte explicity in the presence of other components.
7) LINEARITY:- refers to it’s ability to measure a specific component
within a range.
8) DETECTION LIMIT: the lowest detectable concentration of an analyte
in a sample.
9) QUANTITATION LIMIT:: the lowest measureable concentration of an
analyte in a sample.
10) ROBUSTNESS: ability of a test method to resist the variation in
method parameters ( small variation).
11) RANGE: interval between upper and lower concen. Of analyte.