2. PRESENTATION OVERVIEW
1. Definition
2. Validation, Verification and Qualification
3. Types of Qualification and Qualification
4. Process Validation
5. Stages of Process Validation
6. Types of Process Validation
7. Reason of Process Validation
8. Validation Life Cycle
9. References
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3. Validation:
Action of proving and documenting that any process,
procedure or method actually and consistently leads to the
expectedresults.
Qualification:
Documented evidence that premises, systems or
equipment are able to achieve the predetermined
specifications properly installed, and/or work correctly and
lead to the expected results
Verification:
Verification is the act or process of establishing the truth or
reality of something.
DEFINITION
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4. DEFINITIONS (As per FDA)
Validation means confirmation by examination and
provision of objective evidence that the particular
requirements for a specific intended use can be
consistently fulfilled. [CFR 21 Part 820.3(z)]
Verification means confirmation by examination and
provision of objective evidence that specified
requirements have been fulfilled. [CFR 21 Part 820.3(aa)]
Qualification – NOT DEFINED
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5. DEFINITION (As per WHO)
Validation
Action of proving and documenting that any process, procedure or
method actually and consistently leads to the expected results.
Qualification
Action of proving and documenting that any premises, systems and
equipment are properly installed, and/or work correctly and lead to
the expected results. Qualification is often a part (the initial stage)
of validation, but the individual qualification steps alone do not
constitute process validation.
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6. EXAMPLES
Validation Examples:
Design Validation, Sterilization Validation, Test Method
Validation, Computer System Validation, and Process
Validation.
Verification Examples:
Design Verification and Process Verification.
Qualification Examples:
Installation Qualification, Operational Qualification, Process
Performance Qualification, Product Performance Qualification,
and Supplied Material Qualification
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7. WHY IS VALIDATION REQUIRED?
It would not be feasible to use the equipments without
knowing whether it will produce the product we wanted or
not.
The pharmaceutical industry uses expensive materials,
sophisticated facilities & equipments and highly qualified
personnel.
The efficient use of these resources is necessary for the
continued success of the industry.
Detailed study and control of the manufacturing process –
validation is necessary if failure has to be reduced and
productivity improved.
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8. IS ITONETIMEACTIVITY?
Qualification and validation can not be considered
once-off exercises, For example, the start-up of a new
manufacturing operation.
It is an ongoing programme should follow its first
implementation.
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9. 1. Process validation
a) Prospective Validation
b) Concurrent Validation
c) Retrospective Validation
d) Revalidation
2. Qualification
a) Equipment Qualification
b) Facility Qualification.
c) Utility Qualification.
3. Analytical Method Validation
4. Cleaning Validation
5. Computer System Validation
TYPES OF QUALIFICATION &
VALIDATION
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10. PROCESSVALIDATION
To demonstrate with Documented Evidence that a Specific
‘Manufacturing Process’ is Capable of Performing in a
Reliable and Consistent manner to deliver a homogenous
product meeting defined Quality Attributes Consistently.
Purpose:
High degree of assurance
Consistency
Documented proof
Built-in Quality
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12. STAGES OF PROCESS VALIDATION
Stage 1 – Process Design: The commercial process is defined
during this stage based on knowledge gained through
development and scale-up activities.
Stage 2 – Process Qualification: During this stage, the
process design is confirmed as being capable of reproducible
commercial manufacturing.
Stage 3 – Continued Process Verification: Ongoing
assurance is gained during routine production that the process
remains in a state of control.
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15. PROSPECTIVE VALIDATION
Establishing documented evidence prior to process implementation that a
system does what it proposed to do based on preplanned protocols.
This approach to validation is normally undertaken whenever the process
for a new formula (or within a new facility) must be validated before
routine pharmaceutical production commences.
It is conducted prior to distribution of either a new product or a
product made under a modified Production process, where
modifications are significant and may affect product characteristics
In fact, validation of a process by this approach often leads to transfer of
the manufacturing process from the development function to production.
TYPES OF PROCESS VALIDATION
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16. CONCURRENTVALIDATION
It is establishing documented evidence that a process does
what it purports to do, based on information generated
during actual implementation of the process.
It may be practical approach under certain circumstances.
When a previously validated process is being transferred
to a third party contract manufacturer or to another
manufacturing site .
When number of batches produced are limited.
Revalidation due to changes eg Increase batch size
TYPES OF PROCESS VALIDATION (Contd..)
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17. RETROSPECTIVEVALIDATION
It is establishing documented evidence that a system does what it
purports to do, based on review and analysis of historical
information.
Where the process ; Critical quality attributes and critical
process parameters have been identified; controls have been
established.
There have not been significant process/product failures
attributable to causes other than operator error or equipment
failures unrelated to equipment suitability.
Evaluate : Min 24 batches and Cpk within the limit
TYPES OF PROCESS VALIDATION (Contd..)
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18. REVALIDATION
Revalidation means repeating the original validation effort or
any part of it and includes investigative review of existing
performance data.
This approach is essential to maintain the validated status of
the plant, equipment, manufacturing processes and computer
systems.
Systems and processes should be periodically evaluated
to verify that they are still operating in a valid manner.
Repeated validation of a previously validated system (or a
part thereof) to ensure continued compliance with
establishedrequirements.
TYPES OF PROCESS VALIDATION (Contd..)
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19. Revalidation may be divided into two broad categories:
Revalidation after any change having a bearing on product
quality.
Periodic revalidation carried out at scheduled intervals.
REVALIDATION (Contd..)
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21. PROCESSVALIDATION :PRE-
REQUIREMENT
The following shall be ensured prior to Process
validation;
Facilities, systems and equipment to be used are qualified
Instruments are calibrated
Analytical testing methods are validated.
Process is reviewed and ready (development report with QbD
concept)
Protocol is prepared, reviewed and approved.
Personnel involved in the validation are appropriately trained.21 of 35
22. REASONS FOR REVALIDATION
Possible reasons for starting the process revalidation include:
The transfer of a product from one plant to another.
Changes to the product, the plant, the manufacturing process, the
cleaning process, or other changes that could affect product quality.
The necessity of periodic checking of the validation results.
Significant (usually order of magnitude) increase or decrease in
batch size.
Sequential batches that fail to meet product and process
specifications.
The scope of revalidation procedures depends on the extent of the
changes and the effect upon the product.
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26. SAMPLING
A detailed plan of sampling procedure of samples
which shall be analyzed/monitored during validation
run shall be outline systematically
The sampling plan including sampling points number
of sample and the frequency of sampling for each
stage operation shall be decided based on
characteristic of the product or critical point of
equipment.
Sampling location are to clearly indicate by diagram
for any equipment from which the sample are
withdraw.
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27. SAMPLING TECHNIQUE
Rapid Mix Granulator
T- top M- middle B-bottom
FBD Bowl
Four corner 1,2,3,4
Cone Blende
Top - 1,5,2
Middle - 3,7,4
Bottom - 6,9,8
End - 10
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28. SAMPLING AND ANALYSIS
Stage Sampling Location Test To Be Performed
Dry mixing
3 point from top,3 point from
middle, 3 point from bottom of
bed from RMG
Blend uniformity
Drying Four corner of FBD and middle % % LOD
Lubrication and
Blending
10 samples from top, middle,
bottom
Assay for BU, tapped density
Bulk density, angle of repose
Compression
Draw tablets from compression (10
samples at normal speeds and 1
sample at minimum and maximum
speed
Description, assay, hardness,
thickness, diameter,
friability, weight variation,
CU, disintegration,
dissolution
Coating
Draw tablets from coating pan at
the end of each lot
Same as above and related
substance test
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29. STATISTICS IN VALIDATION
Statistical process control (SPC), also called statistical
quality control and process validation (PV), represents
two sides of the same coin
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30. PROCESS VARIABILITY
The collection and evaluation of information and data about
performance of the process will allow detection of undesired
process variability
Evaluating the performance of the process identifies problem and
determine weather action must be taken to correct anticipate and
prevent problem so that the process remain in control
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31. STATISTICAL TOOL IN VALIDATION
Process Capability
Capability studies are performed to evaluate the ability of a
process to consistently meet a specification.
Capability studies are frequently used towards the end of the
validation to demonstrate that the outputs consistently meet
the specifications. However, they can also be used to study
the behavior of the inputs in order to perform a tolerance
analysis.
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