validation

Presented to:
Prof. H.S. keerthy
Department of Pharmaceutics
MALLIGE COLLEGE OF PHARMACY

Presented By:
Manikant Prasad Shah
Mpharm II Sem.
 WHAT IS VALIDATION?
 According to WHO-
It is the establishment of documented evidence that a
system it is supposed to do.

 According to US FDA-
The process of establishing documented evidence
which provides a high degree of assurance that a
specific process will consistently produce a product
with its predetermined specifications and quality
attributes.
Merits of validation:
1. Assurance of quality compliance.
2. Optimization of resources and manufacture
product at lowest possible cost.
3. Fewer failures, fewer rejects, fewer retests,
fewer reworks, fewer wastage.
4. It is a practice that must be followed for
manufacturing, distribution, selling or license.
5. Efficient production operation.
 Scope of validation:
 Selection of raw material i.e. raw materials of desired quality
attributes
 Product design based on the expected performance
 Process design to build the desired quality attributes in the
product
 Design of control parameters, such as change control, acceptance
criteria, tolerance limits, etc.
 In process quality control parameters and sampling plans
 Finished product testing or evaluation criteria
 Validation of related analytical process
 Validation of related system, facility and equipment
 Personnel training
 Validation involves careful determination of criteria variable of the
process , such as moisture content of granules, drying
temperature of time, etc. and then establishment of acceptable
range and tolerance limit for the same. A careful and continuous
control of these variables will ensure consistent product quality,
Relationship between validation and
qualification:

 Qualification and validation are essentially the same.

The term qualification is normally used for equipment
and utilities, and validation is for systems and
processes. In this sense, qualification can be seen as
part of validation.
Validation Master plan-
 A Validation Master Plan is a document that
summarises the firm’s overall philosophy,
intention and approaches to be used for
establishing performance adequacy.
 A tool to track progress
 Assignment of responsibility and team work
 It identifies acceptance criteria before the start of
validation
V model for validation:
Urs, fat & sat:
 User Requirement Specifications- Manufacturers
should prepare a document that describes, for
example, the utility or equipment to be sourced.
The requirements and specifications for the utility
or equipment should be defined by the user and
documented in the URS.
 Factory Acceptance Test and Site Acceptance
Test- Where appropriate, FAT and SAT should be
performed to verify the suitability of the system at
site, prior to the subsequent stages of
qualification. This should be appropriately
documented.
WHO guidelines for validation of
equipment:
1. All equipment, instruments and other devices used
to measure the physical properties of substances
must be regularly calibrated, validated and verified.
2. Specific procedures must be established for each
type of equipment, instrument and other device,
having regard to the extent to which they are used,
verified and calibrated at regular intervals according
to the SOP.
For example:
(a) pH meters are verified with standard certified buffer
solutions at least once a day;
(b) infrared spectrophotometers require verification at
least once a day and calibration at regular intervals.
3. Only authorized personnel should operate equipment,
instruments and devices. Up-to-date instructions must
be there.
 Includes any relevant manuals (provided by the
manufacturer) must be readily available for use by the
appropriate laboratory personnel (e.g. a copy of these
instructions should be placed beside each apparatus,
together with a schedule of the dates on which it is due
for verification and/or calibration). The results of the
verification must be recorded on a control chart, forming
the basis for the timing of calibration.
4. Each item of equipment, instrument or other device
used for testing, verification and calibration must,
when practicable, be uniquely identified.
5. Records must be kept of each item of equipment, instrument or
other device used to perform testing, verification and/or calibration. The
records must include at least the following:
a) the identity of the equipment, instrument or other device;
b) the manufacturer’s name, the type identification, serial number or
other unique identification;
c) the verification and/or calibration required to comply with the
specifications;
d) the current location, where appropriate
e) the manufacturer’s instructions, if available, or an indication of their
location;
f) the dates, results and copies of reports, verifications and certificates
of all calibrations, adjustments, acceptance criteria, and the due date
of the next verification and/or calibration;
g) the maintenance carried out to date and the maintenance plan;
h) a history of any damage, malfunction, modification or repair.
Types of validation:
Types of validation:
1. Prospective validation-
 Establishing documented evidences during
development stage of process based on a
predefined protocol.
 It is done prior to distribution of a new product or
whenever there is a major change in the product
characteristics.
 Compulsory for sterile products.
 The activity continues till the first 3 batches are
manufactures at full scale.
Steps in prospective validation:
1. Formation of validation team
2. Preparation of validation master plan and validation
protocol
3. Formulation development (preformulation studies and
optimization)
4. Process development (process design, control &
challenges in critical parameters etc.)
5. Facility development (building, support systems, staff)
6. Process qualification (checked for worst case
conditions o ensure reproducibility)
7. Product qualification
8. Change control
2. Concurrent Process validation-
 Carried out during normal production.
 It is useful only if process is well understood
during development stage.
 The nature and specifications of subsequent in-
process and final tests are based on the
evaluation of the results of such monitoring.
3. Retrospective process validation (based on analysis of
historical data)-
 Carried out on the basis of database generated during
previous production of the product.
 Recorded difficulties, variation and failures in production
are analysed to determine the limits of process
parameters.
 Thus, it is useful in establishing priorities for validation.
4. Revalidation-
 It is needed to ensure that the changes in process or in
process environment do not adversely affect the
process characteristic and product quality.
 Revalidation is required when:-
a) There is major change in facility, equipment, process
etc.
b) Periodic revalidation is scheduled at regular interval to
control and identify a gradual change in the process.
Dq, iq, oq, pq processes:
Design qualification-

 Design Qualification protocol is used at the stage

where a design that has been developed from
the VMP / URS / cGMP etc, is reviewed and
documented by competent persons to ensure that
the designed equipment, if built, will satisfy all the
detailed specified requirements, as contained in
the VP and URS.
Installation qualification:
 defined by the FDA as, establishing by objective evidence
that all key aspects of the process equipment and ancillary
system installation adhere to the manufacturer’s approved
specification. It includes:-
I. Examining documentation of equipment design,
identification no., description etc
II. Establishment of critical support system(air, ventilation,
electricity, drainage etc)
III. Ancillary equipments, spare parts are also accounted
IV. Design of SOPs for operation, calibration, maintenance,
cleaning. Reference nos. are given to them.
V. Log books are prepared
VI. Details of the preventive maintenance procedure is
documented.

 Before OQ, IQ datas are reviewed and approved.

 Operational qualification:
 The Operational Qualification Protocol is a collection of test cases
used to verify the proper functioning of a system. The operational
qualification test requirements are defined in the Functional
Requirements Specification. Operational Qualification is usually
performed before the system is released for use. It includes:-
I. Tests are done in normal conditions and worst case conditions
II. Testing procedure is prepared
III. Sampling plan is established and verified using a placebo batch
IV. Checks and calibration of sensors, probes, gauges, recorders,
pressure, temperature etc
V. Requirements for training of personnel involves is identified and
training schedule is finalized and documented.

 The completion of satisfactory IQ and OQ permits a formal release

of equipments for the next stage.
Process qualification:
 Process qualification is the qualification of
manufacturing and production processes to
confirm they are able to operate at a certain
standard during commercial manufacturing.
 Data covering critical process parameters must
be recorded and analyzed to ensure critical
quality attributes can be guaranteed throughout
production.
 Once all processes have been qualified the
manufacturer should have a complete
understanding of the process design and have a
framework in place to routinely monitor
operations. Only after process qualification has
been completed can the manufacturing process
Equipment approval:

 Once approved, the equipment is handed over to

project co-ordinator by project manager.
 All engineering and technical documents are handed
over to the operating department.
Change control:
 Process may be subjected to changes like change in
the spare part of an equipment that can affect product
quality; so criteria for acceptance is decided and its
implementation procedure is established.
References:
 Pharmaceutical Process Validation; Wachter H.
Alfred; Nash Robert; Marcel Dekker Inc.; vol 129;
3rd edition; New York
 http://www.who.int/medicines/areas/quality_safety
/quality_assurance/validation-2016_05_17.pdf
 WHO Technical report, no. 902, 36th report
 Pharmaceutical Master Validation Plan; Haider
Imitiaz;1st Indian Reprint
THANK YOU!