VALIDATION OF

PHARMACEUTICAL
INDUSTRIES
PRIMA RAMADHANI
1111011003
GMP

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.

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.

Elements Of Validation

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

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)

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

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

TYPE OF VALIDATION

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.

 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.

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.

This careful monitoring of the first three production

batches is sometimes regarded as prospective validation.
1

Concurrent validation together with a trend analysis

including stability should be carried out to an appropriate
extent throughout the life of the product.

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.

 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.

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.

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.

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

Process
activities

validation

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.

 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.

PHASES
OF
VALIDATION

PROCESS

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.

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.

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.

 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.

The validation protocol should be numbered, signed

and dated, and should contain as a minimum the
following information:
1.
2.
3.
4.
5.
6.
7.
8.
9.

Title
Objective & Scope
Responsibility
Protocol Approval
Validation Team
Product Composition
Process Flow Chart
Manufacturing Process
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

 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.

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.

THANK YOU