Validation process by Anirban Nandi

1. VALIDATION PROCESS
V A L I D A T I O N B Y A N I R B A N N A N D I ( a n i r b a n b c r c p @ g m a i l . c o m Page 1
INTRODUCTION: - Validation studies are an essential part of GMP and should be conducted in
accordance with predefined protocols. A written report summarizing record results and
conclusion should be prepared and stored. Processes and procedures should be established on the
basis of a validation study and undergo periodic revalidation to ensure that they remain capable
of achieving the intended results. Particular attention should be accorded to the validation of
processing, testing and cleaning procedure. Critical processes should be validated, prospectively
or retrospectively. When any new master formula or method of preparation is adopted, steps
should be taken to demonstrate it is suitability for routine processing. The defined process, using
the materials and equipment specified, should be shown to yield a product consistently of the
required quality. Signification amendments to the manufacturing process include any change in
equipment or materials that may affect product quality and or the reproducibility of the process,
should be validation.
DEFINATION: - Process validation is establishing documented evidence which provides a high
degree of assurance that a specific process (such as the manufacture of pharmaceutical dosage
form) will consistently produce a product meeting its predetermined specification and quality
and characteristics.
PREREQUISITES OF VALIDATION: - More often than not, we use the term validation
generically to cover the entire GMPs aspects which are essentially facility, equipment,
components, procedures and process qualification. The terms process validation should be
reserved for the final stages of the product and process development sequence. Critical stages of
product and process development are laboratory batch (1× size batch) laboratory pilot batch (10×
size batch), pilot production batch (100× size batch). Prerequisites to more formal validation
are:-
**** Process ranging
**** Process characterization
**** Process optimization.
PROCESS CAPABILITY: - Process capability can be defined as the study of critical parameters
or operating variables that influence process output. The objectives of process capability design
and testing are: -
(1) Determination of number of critical parameters in a process that affect the quality of process
output and their relative importance.

2. VALIDATION PROCESS
V A L I D A T I O N B Y A N I R B A N N A N D I ( a n i r b a n b c r c p @ g m a i l . c o m Page 2
(2) To show that the generated numerical data for each critical parameter are within at least
statistical quality control limits ( i.e. ± 3 standard deviation ) and that there is no assignable cause
of variation in the process data.
PROCESS CHARACTERISATION: - How do we find out which process variables and or unit
operation are critical for the product attributes. To find out critical process ranging studies should
be carried out.
PROXESS OPTIMIZATION:- Object of process optimization is to find either best possible
quantitative formula for a product or the best possible set of experimental condition that are
required to carry out the process. Process optimization techniques may be used in the laboratory
stage of development of the product or in the qualification and validation stages of scale-up to
develop the most stable, least variable product or process within its proven acceptable range (s)
of operation (PAR).
**** Selection of suitable experimental design
**** Selection of variables to be tested
**** Performing of a set of statistically designed experiment
**** Measurement of dependent variables.
TYPES VALIDATION: - In fact, there are four options and these are discussed below
**** Prospective process validation
**** Retrospective validation
**** Concurrent validation
**** Revalidation
PROSPECTIVE PROCESS VALIDATION: - In prospective process validation, validation
protocol is executed before process is put in to commercial use (i.e. following trials). This type
of process validation is usually carried out in connection with introduction of new drugs
prospective process validation should be carried out only when the following operation and
procedure have been completed satisfactory:-
**** It should be ensure that facilities and equipment meet GMPs requirement (like this many
point discussed in GMPs book).
RETROSOETIVE VALIDATION: - This option validation is chosen for established product and
where prospective validation cannot be justified for economic considerations and resource
limitations. All equipment, facilities and sub systems should be qualified and validated which

3. VALIDATION PROCESS
V A L I D A T I O N B Y A N I R B A N N A N D I ( a n i r b a n b c r c p @ g m a i l . c o m Page 3
have been used for the production of batches, numerical data of in process and end product
testing of which are to be included in retrospective validation.
CONCURRENT VALIDATION: - In process monitoring of critical processing steps can show
that can be monitored in solid and liquid dosage forms are:-
**** Powder- blend uniformity
**** Moisture content
**** Particle or granules size distribution
**** Weight variation
**** Content uniformity etc.
REVALIDATION: - USFDAs guidelines on general principles process validation recommend
for revalidation whenever there are changes in packing, formulation, equipment, or process
which could have impact on product effectiveness or product characteristics.
CONDITIONS THAT REQUIRE REVALIDATION STUDIES ARE LISTED BELOW:-
**** Changes in critical component
**** Change in facility and or plant
**** Significant change (increase or decrease in batch)
**** Sequential batches that fail to conform product and process specifications.