The document discusses validation of pharmaceutical processes. It describes the key elements of validation including design qualification, installation qualification, operational qualification and performance qualification. It discusses different types of validation such as prospective validation, concurrent validation and retrospective validation. It also discusses revalidation which is needed when any changes are made that could impact quality. The validation process involves three phases - pre-validation, process validation and validation maintenance. A validation protocol and validation master plan are developed to document the validation activities and ensure a systematic approach.

1. VALIDATION OF PHARMACEUTICAL
INDUSTRIES
PRIMA RAMADHANI
1111011003
GMP

2. DESCRIPTION
• As a process of establishing documented
evidence that establishes a high degree of
certainty that a particular process will
consistently a product that provides the
previously established specifications and
quality attributes are available.

3. Validation should thus be considered in the
following situations:
• Totally new process;
• New equipment;
• Process and equipment which have been
altered to suit changing priorities;
• Process where the end-product test is poor
and an unreliable indicator of product quality.

4. Elements Of Validation

5. Design Qualification (DQ)
It is documented review of the design, at an appropriate stage of
stages in the project, for conformance to operational and regulatory
expectations.
DQ Check Items:
• GMPs and regulatory requirements
• Performance criteria
• Facility air flow, movement flow & pressure regimes
• Reliability & efficiency
• Commissioning requirements
• Construct ability & installation of equipment
• Maintenance & access to critical equipment & instrumentation
• Safety & environment impact

6. Installation Qualification (IQ)
It is documented verification that all aspects of a facility, utility or
equipment that can affect product quality adhere to approved
specifications and are correctly installed.
Important IQ considerations are:
• Installation conditions (wiring,utilities, and functionality)
• Calibration, preventative maintenance, cleaning schedules
• Safety features
• Supplier documentation, prints, drawings and manuals
• Software documentation
• Spare parts list
• Environmental conditions (such as clean room requirements,
temperature and humidity)
• Equipment design features (i.e. materials of construction
cleanability)

7. Operational Qualification (OQ)
It is documented verification that all aspects of a facility, utility or equipment
that can affect product quality operate to Intend throughout all anticipated
ranges.
OQ considerations include:
• Process control limits (time, temperature, pressure, line speed and setup
conditions)
• Software parameters
• Raw material specifications
• Process operating procedures
• Material handling requirements
• Process change control
• Training
• Short term stability and capability of the process, (latitude studies or
control charts)
• Potential failure modes, action levels and worst-case conditions (Failure
Mode and effects
• Fault tree analysis

8. Performance Qualification (PQ)
It is documented verification that all aspects of a
facility, utility or equipment perform as intended in
meeting predetermined acceptance criteria.
PQ considerations include:
• Actual product and process parameters and
procedures established in OQ
• Acceptability of the product
• Assurance of process capability as established in
OQ
• Process repeatability, long term process stability

9. TYPE OF VALIDATION

10. Prospective validation
• 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
situations.

11. • Where possible critical situations are identified, the
risk is evaluated, the potential causes are investigated
and assessed for probability and extent, the trial plans
are drawn up, and the priorities set.
• The trials are then performed and evaluated, and an
overall assessment is made.
• If, at the end, the results are acceptable, the process is
satisfactory.
• Unsatisfactory processes must be modified and
improved until a validation exercise proves them to be
satisfactory.
• This form of validation is essential in order to limit the
risk of errors occurring on the production scale, e.g. in
the preparation of injectable products.

12. Concurrent validation
• Concurrent validation is carried out during normal
production. This method is effective only if the
development stage has resulted in a proper understanding
of the fundamentals of the process.
• The first three production-scale batches must be monitored
as comprehensively as possible.
• 1The nature and specifications of subsequent in-process
and final tests are based on the evaluation of the results of
such monitoring.
• 1 This careful monitoring of the first three production
batches is sometimes regarded as prospective validation.
•
Concurrent validation together with a trend analysis
including stability should be carried out to an appropriate
extent throughout the life of the product.

13. Retrospective validation
• 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
analysed to determine the limits of process parameters.
• A trend analysis may be conducted to determine the extent
to which the process parameters are within the permissible
range.
• Retrospective validation is obviously not a quality
assurance measure in itself, and should never be applied to
new processes or products. It may be considered in special
circumstances only, e.g. when validation requirements are
first introduced in a company.

14. • Retrospective validation may then be useful in
establishing the priorities for the validation
programme.
• If the results of a retrospective validation are positive,
this indicates that the process is not in need of
immediate attention and may be validated in
accordance with the normal schedule.
• For tablets which have been compressed under
individual pressure-sensitive cells, and with qualified
equipment, retrospective validation is the most
comprehensive test of the overall manufacturing
process of this dosage form.
• On the other hand, it should not be applied in the
manufacture of sterile products.

15. Revalidation
• Revalidation is needed to ensure that changes in the
process and/or in the process environment, whether
intentional or unintentional, do not adversely affect
process characteristics and product quality.
• Revalidation may be divided into two broad categories:
1. Revalidation after any change having a bearing on
product quality.
2. Periodic revalidation carried out at scheduled
intervals.

16. 1. Revalidation after any change
having a bearing on product quality.
• Revalidation must be performed on introduction of any
changes affecting a manufacturing and/or standard
procedure having a bearing on the established product
performance characteristics.
• Such changes may include those in starting material,
packaging material, manufacturing processes,
equipment, in-process controls, manufacturing areas,
or support systems (water, steam, etc.).
• Every such change requested should be reviewed by a
qualified validation group, which will decide whether it
is significant enough to justify revalidation and, if so, its
extent.

17. 2. Periodic revalidation carried out at
scheduled intervals.
• It is well known that process changes may occur gradually
even if experienced operators work correctly according to
established methods.
• Similarly, equipment wear may also cause gradual changes.
• Consequently, revalidation at scheduled times is advisable
even if no changes have been deliberately made.
• The decision to introduce periodic revalidation should be
based essentially on a review of historical data, i.e. data
generated during in-process and finished product testing
after the latest validation, aimed at verifying that the
process is under control.
• During the review of such historical data, any trend in the
data collected should be evaluated

18. Process validation activities

19. Process validation is defined as the collection
and evaluation of data, from the process
design stage throughout production, which
establishes scientific evidence that a process is
capable of consistently delivering quality
products.

20. • Stage 1 - Process Design: The commercial process
is defined during this stage based on 100
knowledge gained through development and
scale-up activities.
• Stage 2 - Process Qualification: During this stage,
the process design is confirmed as 103 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.

21. PHASES OF PROCESS VALIDATION

22. Phase 1
• Pre-Validation Phase or the Qualification Phase,
which covers all activities relating to product
research and development, formulation, pilot
batch studies, scale-up studies, transfer of
technology to commercial scale batches,
establishing stability conditions, storage and
handling of in-process and finished dosage forms,
equipment qualification, installation qualification,
master production documents, operational
qualification, process capability.

23. Phase 2
• Process Validation Phase (Process
Qualification phase) designed to verify that all
established limits of the critical process
parameters are valid and that satisfactory
products can be produced even under the
"worst case" conditions.

24. Phase 3
• Validation Maintenance Phase requiring
frequent review of all process related documents,
including validation audit reports to assure that
there have been no changes, deviations, failures,
modifications to the production process, and that
all SOPs have been followed, including Change
Control procedures.
• At this stage the validation team also assures that
there have been no changes/ deviations that
should have resulted in requalification and
revalidation.

25. • The validation protocol provides a synopsis of
what is hoped to be accomplished.
• The protocol should list the selected process
and control parameters, state the number of
batches to be included in the study, and
specify how the data, once assembled, will be
treated for relevance.
• The date of approval by the validation team
should also be noted.

26. The validation protocol should be numbered, signed and dated,
and should contain as a minimum the following information:
1. Title
2. Objective & Scope
3. Responsibility
4. Protocol Approval
5. Validation Team
6. Product Composition
7. Process Flow Chart
8. Manufacturing Process
9. Review of Equipments /
Utilities
10.Review of Raw Materials and
Packing Materials
11. Review of Analytical and
Batch Manufacturing Records
12. Review of Batch Quantities for
Validation (Raw Materials)
13. Review of Batch Quantities for
Validation (Packing Materials)
14. HSE Requirements
15. Review of Process Parameters
16. Validation Procedure
17. Sampling Location
18. Documentation
19. Acceptance Criteria
20. Summary
21. Conclusion

27. • Validation Master Plan is a document that
summarizes the company's overall philosophy,
intentions and approaches to be used for
establishing performance adequacy. The
validation master plan should be agreed upon by
management.
• The validation master plan should provide an
overview of the entire validation operation, its
organizational structure, its content and planning.
The main elements include the list/inventory of
the items to be validated and planning schedule.

28. The format and content should include
• Introduction: validation policy, scope, location and schedule
• Organizational structure: personnel responsibilities
• Plant/ process /product description: rational for inclusions
or exclusions and extent of validation
• Specific process considerations that are critical and those
requiring extra attention
• List of products/ processes/ systems to be validated,
summarized in a matrix format, validation approach
• Re-validation activities, actual status and future planning
• Key acceptance criteria
• Documentation format
• Reference to the required sop's
• Time plans of each validation project and sub-project.

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