This document discusses validation in the pharmaceutical industry. It begins by defining validation as a series of actions to prove that any process or system performs its intended functions adequately and consistently. It then discusses why validation is needed, including to ensure quality, comply with regulations, and avoid recalls. The document also covers validation teams, master plans, protocols, and the key elements of validation including process qualification.

1. Preswnted By:
Atul Adhikari
M.Pharm 1st semester,
Assam Down Town University, Guwahati
Guided By:
Ananta Choudhury
Department of Pharmacy, ADTU

2.  What is Validation?
 When it is needed?
 Why it is needed?
 Validation team
 Validation Master Plan
 Validation Protocol
 Elements of Validation(PQ, IQ, OQ, DQ)
 Dosage form Validation
Department of Pharmacy, Assam Down Town University. 2

3.  Documented series of action that prove that
 any procedure, process, equipment,
materials, activities or systems performs its
intended functions;
 Adequately and consistently
 And lead to the expected results of uniform
batches that meet the required
specifications and quality attributes.
3Department of Pharmacy, Assam Down Town University.

4.  Essential and integral part of GMP
 Fundamental to achieve the principle of QA.
 Documentation associated with validation
includes a quality manual, SOPs,
specifications, Validation Master Plan(VMP),
Validation and Qualification protocols,
Validation and Qualification reports.
4Department of Pharmacy, Assam Down Town University.

5.  Totally new process
 New equipments
 Process and equipments which are altered to
suit changing priorities.
 Process where end product test is poor and
unreliable indicator of product quality.
5Department of Pharmacy, Assam Down Town University.

6.  Control of all critical process parameters,
results of IPQC, final quality control, and
stability tests.
 At least three batches (including at least two
production batches in the final batch size)
should be validated to show consistency.
6Department of Pharmacy, Assam Down Town University.

7.  Worst case situations should be considered.
 A condition or set of conditions encompassing
upper and lower processing limits and
circumstances within SOPs which posses
greatest chances of product or process
failure when compared to ideal conditions.
7Department of Pharmacy, Assam Down Town University.

8.  Fewer batch failure.
 Process may operate more efficiently.
 Greater output
 Commitment to product quality
 Facilitate pre-approval inspections
 Higher chances of granting marketing
authorization.
 Reduce the dependence on intensive IPQC
and final control.
8Department of Pharmacy, Assam Down Town University.

9. Includes personnel from:
 QA
 Production
 QC
 Maintenance
 Finance
9Department of Pharmacy, Assam Down Town University.

10.  Should meet regularly with defined schedule
to discuss issues relating to validation and
access progress and compliance with the
validation plan and schedule.
 Maintain records of meeting and inform the
management of progress.
10Department of Pharmacy, Assam Down Town University.

11.  VMP complements the manufacturer’s site
master file and should be the first document
to be reviewed during inspection by a
regulatory authority.
 VMP reinforces the commitment of the
company to GMP.
 Formal policy document which describes the
overall philosophy of the company towards
validation.
11Department of Pharmacy, Assam Down Town University.

12.  It describes the key elements of the
validation programme, organizational
structure of validation, schedules and
responsibilities.
 It should describe:”Why, What, Where, by
whom, how and when?”
12Department of Pharmacy, Assam Down Town University.

13. VP should describe clearly the procedure to be
followed for performing validation.
VP should include:
 Background information
 Objectives of validation and qualification
 Site of study
 Responsible personnel
 Description of SOPs to be followed.
 Equipments
 Standards and criteria for the relevant products
and processes
 Type of validation
 And frequency
13Department of Pharmacy, Assam Down Town University.

14. 1. Design Qualification (DQ)
Documented review of the design, at an appropriate
stage in the project, to conform the operational
and regulatory requirements.
DQ check items:
 GMP and regulatory requirements
 Performance criteria
 Facility air flow, movement flow and pressure
regimes.
 Reliability and efficiency.
 Construct ability and installation of euipments
 Maintainance and acess to critical equipments and
instrumentation.
 Safety and environment impact.
14Department of Pharmacy, Assam Down Town University.

15.  Documented verifications that all aspects of a facility,
utility or equipment that can affect product quality adhere
to approved specifications and are correctly installed.
 IQ considerations:
 Installation conditions of wires, utilities
 Calibrations, preventative maintenance, cleaning
schedules
 Safety features
 Supplier documentation, prints, drawing and manuals.
 Software documentations
 Spare part list
 Environment conditions( temperature, humidity)
 Equipment design features( materials of construction,
cleanability)
15Department of Pharmacy, Assam Down Town University.

16.  Documented verification that all aspects of a facility,
utility or equipment that can affect product quality
operate to intended specifications and control.
 OQ considerations include:
 Process control limits( time, temperature, pressure,
etc)
 Software parameters
 Raw materials parameters
 Process operating procedures
 Materials handling requirements
 Process change control
 Training
 Short term stability and capability of the process
 Potential failure modes, mechanisms and worst case
scenario
16Department of Pharmacy, Assam Down Town University.

17.  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.
17Department of Pharmacy, Assam Down Town University.

18.  “QUALITY IS NOT TESTED INTO A PRODUCT
BUT RATHER IS BUILT IN”
 Product validation is a systematic approach
to identify, measure, evaluate, document,
re-evaluate a series of critical steps in the
manufacturing process that require control
to ensure a reproducible final product.
Department of Pharmacy, Assam Down Town University. 18

19.  Legally, manufacturers must conform to
cGMP regulations.
 Good business: validation means avoiding the
possibility of product recalling or rejection.
 Validation helps to ensure product uniform
reproducibility and quality.
Department of Pharmacy, Assam Down Town University. 19

20. a. Validation of raw materials
b. Analytical Methods Validation
c. Equipment/Facility Validation
d. Process Validation
Department of Pharmacy, Assam Down Town University. 20

21.  Both API and excipients
 Preformulation phase of product
development is more critical step in
developmental cycle.
 Particle size, shape, and density of drug can
affect material flow and blend uniformly.
Factors to be considered:
 grade and source of materials
 Particle size and shape characteristics
 Lot-to-lot variability
Department of Pharmacy, Assam Down Town University. 21

22.  Each raw material validated by checking on
several batches(at least three)from the primary
as well as alternative supplier.
Steps are:
1. Physical, Chemical and/or microbiological
stability to be measured.
2. Once (1) is passed, used for manufacturing of
final product and evaluate for effect of small
change in concentration of exipients on
product stability.
3. On-site inspection of supplier to review the
vendor’s manufacturing operations and control
procedures.
Department of Pharmacy, Assam Down Town University. 22

23.  Analytical criteria for validation:
1. Accuracy of method: ability of method to measure
the true value of a sample.
2. Precision of method: ability of method to estimate
reproducibility of any given value but not
necessarily the true value.
3. Specificity: ability to accurately measure the
analyte in presence of other components.
4. In-day/In-out Variation: does the precision and
accuracy change when conducted numerous times
on same day and repeated on subsequent day?
5. Between operator variation
6. Between instruments variation
7. Between laboratory variation.
Department of Pharmacy, Assam Down Town University. 23

24.  Process equipments used in the development
phase is assessed relative to its suitability for
large-scale manufacture.
 Alternative equipment is identified and
evaluated.
 Existing or new equipment to be used to
manufacture the new pharmaceutical
product must then undergo a comprehensive
evaluation called a validation protocol.
 The protocol can be divided into different
components(DQ, IQ, OQ, PQ)
Department of Pharmacy, Assam Down Town University. 24

25.  Means of challenging a process during
development to determine which
variables must be controlled to ensure
the consistent production of products and
intermediates.
 The information gathered in all stages is
evaluated to determine which parameters
in the process can be used as possible
tools to show that the product is under
proper control.
Department of Pharmacy, Assam Down Town University. 25

26.  Other major steps in the development of validation
program are:
1. Obtaining test data to determine the numerical
range of each parameter. eg: access hardness of
tablet over a series of batches that achieves an
acceptable friability, disintegration, and
dissolution.
2. Establishing specification limits from the test data
derived for a given parameter. Based on the data
collected and using statistical techniques determine
the extremes of acceptable hardness (high and low)
3. Determining how well the specification limit
indicates that the process is under control.
4. Certifying the equipment that is used in obtaining
the data and controlling the process. Ensure that
equipment operating condition (eg: rpm, temp,etc)
are within specfication limits under variations of
product load.
Department of Pharmacy, Assam Down Town University. 26

27.  Validation of new process
Department of Pharmacy, Assam Down Town University. 27

28. Department of Pharmacy, Assam Down Town University. 28

29. a. Tablet composition: identify the key
physiochemical properties of the drug
substance that need to be considered in
developing the formulation, such as following:
 Solubility of drug substance throughout the
physiological pH range
 Particle size distribution and surface area
 Morphology
 True and bulk density
 Material flow and compressibility
 Hygroscopicity
 Melting point
Department of Pharmacy, Assam Down Town University. 29

30. b. Process evaluation and selection: Determine
the unit operations needed to manufacture
the tablets.
 Mixing or blending
 Wet granulation
 Wet milling
 Drying
 Milling
 Tablet compression
 Tablet coating
Department of Pharmacy, Assam Down Town University. 30

31. c. Equipment Evaluation: Following items to be
considered when evaluating equipment for
the manufacture of tablet dosage form:
 Mixer/granulator
 Blender
 Dryer
 Mills
 Tablet compressor
 Tablet coater
Department of Pharmacy, Assam Down Town University. 31

32. Tablet Compressor:
 How many compression station?
 Operating range (rpm)?
 Output range of compressor? (tab/min)
 Type of powder feeding capabilities?
 Compression force range?
Department of Pharmacy, Assam Down Town University. 32

33.  www.who.org
 www.pharmaguideline.com
 Supplementary Guidelines on GMP by WHO
Department of Pharmacy, Assam Down Town University. 33