Validation history definition importance and scope.

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SUHASINI NAYAL
(MQA 202 T)

2. CONTENT
 HISTORY
 DEFINITION
 IMPORTANCE
 SCOPE
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3. HISTORY
 The concept of validation was first proposed by two Food and
Drug Administration (FDA) officials, Ted Byers and Bud Loftus, in
the mid 1979s in(USA )order to improve the quality of
pharmaceuticals. It was proposed in direct response to several
problems in the sterility of large volume parenteral market. The
first validation activities were focused on the processes involved in
making these products, but quickly spread to associated processes
including environmental control, media fill,
equipment sanitization and purified water production.
 The concept of validation was first developed for equipment and
processes and derived from the engineering practices used in
delivery of large pieces of equipment that would be manufactured,
tested, delivered and accepted according to a contract The use of
validation spread to other areas of industry after several large-
scale problems highlighted the potential risks in the design of
products.
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4.  The most notable is the Therac-25 incident . Here, the
software for a large radiotherapy device was poorly designed
and tested. In use, several interconnected problems led to
several devices giving doses of radiation several thousands of
times higher than intended, which resulted in the death of
three patients and several more being permanently injured.
 In 2005 an individual wrote a standard by which the
transportation process could be validated for cold chain
products. This standard was written for a biological
manufacturing company and was then written into the PDA's
Technical Report # 39, thus establishing the industry standard
for cold chain validation. This was critical for the industry due
to the sensitivity of drug substances, biologics and vaccines to
various temperature conditions. The FDA has also been very
focused on this final area of distribution and the potential for a
drug substances quality to be impacted by extreme
temperature exposure.
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5. HISTORY
 1978 GMP include validation
 1987 First Validation Guidance ( Equipment IQ)
 2000 New approaches/ Documents / Presentations
 2008New Process validation Draft Guidance(Equipment
and Analytical Validation)
 2007New Process Validation Guidance Issued
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6. Definition
 According to the Food and Drug Administration (FDA),
“establish documented evidence which provides a high degree of
assurance that a specific process will consistently produce a
product meeting its predetermined specifications and quality
attributes.”
 ISO definition :Validation is the confirmation by examination
and the provision of objective evidence that the particular
requirements for a specific intended use are fulfilled.
 According to European commission “Action providing in
accordance with the principles of GMP ,that any procedure ,
process , equipment , material , activity or system actually lead to
the expected results.
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7.  Validation is the documented act of proving that any procedure,
process, equipment, material, activity or system actually leads to
the expected result.
 Validation can be defined as a procedure that demonstrates that
a process under standard conditions is capable of consistently
producing a product that meets the established product
specifications. Validation refers to the practice of documenting
and proving that a procedure or process consistently leads to the
expected results. This is a good manufacturing practice where
data is collected and analyzed to verify that a process operates
within the set parameters. The validation process is done to
prove the consistency of the expected results of any process,
procedure or method. Additionally, it verifies that the quality
standards and compliance are being met by the products in real-
time. The validation program assures that a pharmaceutical
facility is meeting the pharmaceutical cGMP guidelines as set for
the industry by the regulatory bodies.
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8. IMPORTANCE
1. Assurance of quality
2. Time bound
3. Process optimisation
4. Reduction of quality cost.
5. Nominal mix-ups, and bottle necks
6. Minimal batch failures, improved efficiently and productivity.
7. Reduction in rejections.
8. Increased output.
9. Avoidance of capital expenditures
10. Fewer complaints about process related failures.
11. Reduced testing in process and in finished goods.
12. More rapid and reliable start-up of new equipments 8

9. 13. Easier scale-up form development work.
14. Easier maintenance of equipment.
15. Improved employee awareness of processes.
16. More rapid automation.
17. Government regulation (Compliance with validation
requirements is necessary for obtaining approval to manufacture
and to introduce new products.
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10. Scope of validation:-
 It is very vast area validation system includes :-
 Analytical method validation:-The analytical test method requires
demonstration of the following characteristics in validation.
 Accuracy
 Precision
 Specificity
 Limit of detection
 Limit of quantification
 Linearity
 Range
 Ruggedness
 Robustness
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11.  Instrumental calibration:-Measurement of various
parameters in a prime activity in pharmaceutical
processing and hence , it demands a very high level of
accuracy in such measurements . Some of the common
measurements involved are temperatures , pressure ,
relative , humidity , time , rotations , current , voltage
weights and so on .All devices which are used to measure
such parameters requires calibration of these devices so
that the level of confidence in the measurements and also
in the process becomes very high.
 The calibration is carried out in the beginning of the
validation activities.
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12.  Process utility services :- support the manufacturing
process and the plant is required to operate them regularly.
 Some of the important process utility services are as
follows:-
 Different types of water : raw water , portable water,
purified water, water for injection, soft water.
 HVAC system: heating , ventilation , air conditioning.
 Different gases: L.P.G , oxygen , carbon dioxide .
 Drainage system.
 The validation of these process utility services are done.
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13.  Raw materials and Packaging materials
 1) Validation begins with the raw materials, active
pharmaceutical ingredients excipients . Raw material is
major causes of product variation or deviation from
specification .Qualification of R.M / P.M requires two
stage programme.
 Stage1 : Defining specifications for each and every item of
R.M/P.M such that it meets the product and process
requirements.
 Stage2 : Vendor certification- to study and certify vendor
who can supply you the desired quality of materials ,in
required quantities at expected time and at affordable
price.
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14.  Equipment validation
 Validation of equipment includes the qualification of the
equipment which entails
 Design Qualification - DQ,
 Installation Qualification - IQ,
 Operational Qualification - OQ
 Performance Qualification - PQ.
 Validation also includes training, SOPs on operation,
cleaning, maintenance, calibration
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15.  cleaning validation program in place to establish
documented evidence that the cleaning processes will
consistently ensures that the products produced will meet
expectations for purity, identity, safety and quality. The
purpose of cleaning validation is to ensure that no
significant amounts of active ingredients or excipients
carry over into subsequent uses of the equipment.
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16.  Process Validation is the analysis of data gathered
throughout the design and manufacturing of a product in
order to confirm that the process can reliably output
products of a determined standard. Regulatory authorities
like EMA and FDA have published guidelines relating to
process validation. The purpose of process validation is to
ensure varied inputs lead to consistent and high quality
outputs. Process validation is an ongoing process that must
be frequently adapted as manufacturing feedback is
gathered. End-to-end validation of production processes is
essential in determining product quality because quality
cannot always be determined by finished-product
inspection. Process validation can be broken down into 3
steps: process design, process qualification, and continued
process verification .
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17.  Design validation The approach to validating the new design or
design revision needs to be clearly defined, documented and
approved in advance of commencing a design activity. Validation
should be performed on sample lots, prior to actual production
runs . The design validation should confirm that the product or
process conforms to customer requirements . The validation
should include testing under expected operating conditions plus
testing to the allowed limits of use . Validation should cover all
design outputs, based on potential risk. For example, if incorrect
labels could post a risk to consumers, then the label manufacture
and control process should be validated. If a risk assessment
deems that verification would be an in-adequate control or if
verification is not to be performed due to cost considerations,
then validation needs to be performed . The results obtained from
all validation activity, should be documented, and maintained in
the design history file. The file does not need to physically contain
all documentation, but should point to where such
documentation can be obtained . It is important to ensure that a
comprehensive records storage, archiving and maintenance
process is established to ensure that validation results can be
readily retrieved even when performed years previous. 17

18.  Validation requires an appropriate and sufficient
infrastructure including: organization, documentation,
personnel and finances
 Involvement of management and quality assurance
personnel
 Personnel with appropriate qualifications and experience
 Validation is performed: for new premises, equipment,
utilities and systems, and processes and procedures; at
periodic intervals; and when major changes have been
made.
 Significant changes (facilities, equipment, processes) -
should be validated
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19. THANK YOU
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