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Validation|Process validation
Validation is one of the most important and common terms used in pharmaceutical industries
and its simple meaning is to provide a high degree of assurance or confirmation regarding
product quality and system reliability

The concept of validation gives a high level of assurance that products manufactured in
pharmaceutical industries are fit for use and the same quality is maintained in all batches of the
product.
In this article,we will learn about,

 History
 What is Validation?
 Importance of Validation
 Process Validation
 Guidelines & Definitions
 Types Of Process Validation
 What is Prospective Validation?
 When To Perform Prospective Validation?
 What to Do in Prospective Validation?
 What is Concurrent Validation?
 When To Perform Concurrent Validation?
 What to Do in Concurrent Validation?
 What is Retrospective Validation
 When To Perform Retrospective Validation?
 What to Do in Retrospective Validation?
 What is Re-Validation
 When To Perform Re-Validation?
 What to Do in Re-Validation?
 Cleaning Validation
 Method Validation
 Computer Validation
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History
 The concept of Validation in pharmaceutical industries was introduced by FDA due to the
problems in the sterility of parenteral products.
It was first adopted for the processes but later on,it spread to the following,

 Equipment
 Media fill
 Purified water production
 Environment control etc.

Pharmaceutical Validation
In pharmaceutical industries,Validation is a documented evidence to demonstrate that all the
processes, system,utility or facility are designed in such a way that they produce the same
results on repeated usage.
To understand the pharmaceutical validation simply and easily we can say that validation
means to get the same output results for all pharmaceutical products and systems at different
time intervals provided that the input should remain the same.

Explanation
Suppose we manufacture a tablet product by wet granulation method using a specific
procedure,formulation,area and equipment
etc.
During first manufacturing we will check and perform analysis of all critical steps during
granulation to observe the results of the product and when we complete our three batches with
the same quality using same input we declare that our product is now validated and we can get
same quality of product using same input unless and until we do not change any input value.

Importance Of validation
 Validation ensures the product quality.
 Validation reduces the chances of non compliance.
 Validation reduces the chances of product recall.
 Data of validation acts as proof in making decisions.
 During inspection validation data gives assurance to the inspecting bodies that the
procedures are reliable.
 Meet regulatory requirements.
 Cost of manufacturing is reduced due to less testing because once the product is
validated we do not require intensive testing on all the stages.
 The pharmaceutical industries which do not have a validation system for manufacturing
perform testing on all the stages,means after granulation they have to perform the analysis of
blend to ensure that the assay of the product is in the range.
 After analysis of blend they compress the tablets and after compression again testing is
performed for content uniformity,assay,dissolution and
disintegration etc.
 In the same manner again testing is required after coating.
 The product is then packed and testing is done for the finish product before its dispatch
to the finish good store.
 We repeat testing on all stages because our process is not validated and it makes our
process costly.
 Once we validate our process then intensive testing is not required. We build quality in
our product by using validated procedures and testing is done only at critical steps which
reduces the cost.

Types of Validation
There are following types of validation
 Process Validation
 Cleaning Validation
 Method Validation
 Computer validation
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Process Validation
It is an establishment of documented evidence which gives assurance that a process will
continuously produce a product having predetermined specifications and quality attributes.
 Validating each individual step of a process is known as process validation in the
pharmaceutical industry.

Guidelines for Process Validation

 The concept of process validation was first introduced by the US FDA in 1978.
 (cGMP) of finished products give details of validation.

US FDA Definition
US FDA defines the process validation as follow,
 It is establishing documented evidence(prove)which provides a degree of assurance that
a specific process will consistently produce a product meeting its predetermined specifications
and Quality characteristics.

ICH Definition
 According to ICH It is the process of ensuring and providing documentary evidence that
processes within their design parameters are capable of repeatedly and reliably producing a
finished product of the required quality.

WHO Definition
 The documented action of proving that any
procedure,process ,equipment,material,activity or system actually leads to the expected result.

Explanation
 Process validation in pharmaceutical industries starts from the initial developmental
stage in research and development and continues till its shelf life in the market to provide
assurance of a finished product even after its dispatch to the market.
 When a pharmaceutical company is going to manufacture a new product it has no
documents for its manufacturing and testing.
 The development of all the procedures for testing and manufacturing which ensures
product quality is known as process validation and method development.
 When the product is manufactured using the developed procedure and its quality and
efficacy is tested by using the analytical method which was developed,we claim that our process
for manufacturing and testing is validated.

Also Read
Qualification|FAT|SAT|DQ|IQ|OQ|PQ

When to perform Process Validation?

Process validation is performed in case of following,

 For manufacturing new products.

 In case of any change in the manufacturing process which has a major effect on product
quality.
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Types Of Process Validation

Process validation in pharmaceutical industries are of following types

1. Prospective Validation
2. Concurrent Validation
3. Retrospective Validation
4. Revalidation

1.Prospective Validation
 Prospective validation is establishing documented evidence that a system performs as it
is intended based on pre-planned protocol.(Before process implementation).
 Prospective validation is performed in a research and development lab on a small scale.

When To Perform
 Prospective validation is performed for developing new products.
 Prospective validation is performed if we make any change in the manufacturing process
which has a major effect on the product quality.
 This type of validation is performed before starting the routine batches of production.
 Prospective validation is performed at the stage of product development.
 In this type of validation all the process is divided into different steps and each step is
monitored critically.
 The impact of different parameters is observed.

What to Do in Prospective Validation?

 As we know, prospective validation is carried out in the research and development stage
so its start from developing formulation.
 Formulation of a new product is developed at this stage.
 Specification of raw materials are defined.
 Procedure for manufacturing is developed in the form of validation protocol.
 Procedure for cleaning validation is defined.
 All the critical points are observed on risk based analysis.
 Process parameters like mixing time,drying time etc are defined and adjusted to get
desired results.
 Batch Manufacturing Record is prepared.
 Testing method for analysing the product is developed.
 Sampling plan is prepared.
 Technology transfer documents are prepared.
 Environmental factors like temperature and humidity and storage conditions are defined.

Results
 Usually three batches are manufactured at this stage and all should produce desired
results using the same parameters.
 If we have to make changes in parameters of the first batch to adjust the results,these
changes are made through proper change control procedure.
 The batch in which we make changes will not be considered the validation batch.
 We will have to take the next three batches with the same parameters to build
confidence that our procedures and methods are reliable.
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2.Concurrent Validation
 The word concurrent can be remembered by a simple word current,which means this
type of validation is performed on current production batches.
 Concurrent validation is performed in the production area after getting satisfying results
of prospective validation.
 In concurrent validation the product is manufactured in the production area using the
production facility and equipment.

When to Perform Concurrent?

Concurrent validation is performed in following,

 Product which has completed its prospective stage,is validated in the production area
during concurrent validation.
 When there is a change in process which has no significant effect on product quality.
 Change in a raw material source.
 When a validated batch is required to be manufactured in other facilities(Plant) then no
need to perform prospective validation only to do is to perform concurrent validation.
 When there is change in equipment used.
 When there is only change in tablet strength and previous strength was validated by the
prospective validation and change strength has the same ratio of API and Excipients.

What to Do?
 Before starting the concurrent validation it is ensured that the operators involved in the
manufacturing process are trained.
 All the equipment,utility and systems are qualified.
 Three batches are manufactured to ensure the same product quality.
 In concurrent validation all the critical parameters of batches which are under
manufacturing are observed.
 All the parameters are adjusted according to prospective validation.
 Sampling plan is followed as provided by the product development department.

Summery
In concurrent validation we manufacture the large scale batches using the same parameters as
manufactured in small scale during prospective validation to ensure that our process developed
is capable of producing the quality results.
 Samples are checked at specified time intervals.
 Prospective validation is done for three batches.
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Also Read
100 MCQs to revise your pharmaceutical knowledge.

3.Retrospective Validation
Retrospective validation is documented evidence that products manufactured in the
pharmaceutical industry using validated procedure maintain its quality and purity in the market
during the period of its shelf life.
Retrospective validation is performed after the dispatch of product in the market.
What to Do?
 In the pharmaceutical industries the reference samples are withdrawn from the finish
product batches before its dispatch to the market.
 After the specified time period the sample is taken from the reference samples and is
tested.
 It is done to ensure that our product in the market is still meeting a quality attribute
during its shelf life.
Following type of data is also collected during Retrospective validation,
 Number of batches manufactured for a defined period of time.
 Batch size
 Strength of the product.
 Manufacturing and expiry date of the product.
  Master documentation.
 List of deviations and corrective actions.
 Stability testing data for different batches.
It is used for audits of validated processes.

4.Re-Validation
Validation is done once in the product life cycle until there is no change in the product
manufacturing parameters.
In some specific circumstances we have to revalidate our products.

When To Re-validate
The revalidation of process is required in following cases,

 When there is a change in critical parameters.

 When there is a change in product formulation.
 When there is a change in the product process.
 When there is a change in equipment.
 When there is a change in the facility.
 When there is a change in primary packaging.
 When there is a change in raw material density,particle size etc.
 Source change of API.
 Change in any process parameter like mixing time,drying temp,etc
 When there is a change in batch size.
 When there is a change in the plant.(Shifting from one plant to other)
 Periodically checking the validation results.
 When the product fails to meet the specification.

Also Read
Pharmaceutical Questions and Answers.

Cleaning Validation
 Cleaning validation is documented evidence that method developed for cleaning is
capable of removing the chemical,biological residues and all traces of excipients, API and
detergent are properly removed.

Read More
Cleaning Validation In Pharmaceutical Industry

Method Validation
Method validation is documented evidence that the method developed for analysis of
pharmaceutical products is suitable for producing the desired results.

Computer Validation
Computer validation is documented evidence that all the computer-based operations will
produce the desired results.

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About Author

Sajjad Ahmad
Sajjad Ahmad is a young Pakistani Pharmaceutical Blogger.He has spent
more than a decade in different Pharmaceutical Industries.Currently he is
working as a Production Manager in a well Reputed Pharmaceutical
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