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PHARMACEUTICAL
VALIDATION
PRESENTED BY:
BHARATLAL SAIN
1ST M.PHARM
PHARMACEUTICS
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CONTENTS

 INTRODUCTION
 OBJECTIVE
 IMPORTANCE
 VALIDATION MASTER PLAN
 CALIBRATION MASTER PLAN
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INTRODUCTION

DEFINITION:
According to FDA:
“Establishing the documented evidence which provides a high degree of assurance
that a specific process will consistently produce a product of predetermined
specifications and quality attributes”.
OR
“Process validation is defined as the collection and evaluation of data, from the
process design stage to commercial production, which establishes scientific evidence
that process is capable of consistently delivering quality product”.
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According to EU GMP:
“Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment,
material, activity or system actually leads to expected results”.

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.
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OBJECTIVES

 To reduces risk of regulatory non-compliance.

 Reduction of time to the market for the new products.
 Eliminates the scrap & reduces the defect cost.
 To reduce chances of product re-call from market.
 The final release of the product batch would be expedited.
 It requires less in-process control & end process testing.
 Parametric release of batch can be achieved in validation.
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SCOPE OF VALIDATION

 Pharmaceutical Validation is a vast area of work and it practically covers every aspect of pharmaceutical processing activities,
hence defining the Scope of Validation becomes a really difficult task. However, a systematic look at the pharmaceutical
operations will point out at least the following areas for pharmaceutical validation.
 Analytical
 Facilities
 Manufacturing operations
 Product Design
 Cleaning
 Instrument Calibration
 Process Utility services
 Raw materials
 Packaging materials
 Equipment
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MERITS OF VALIDATION

 Knowledge of the process increases during the validation process.

 Consistency of the process is ensured.
 It decrease the risk of the manufacturing problems.
 Ensures the fluency of the production.
 Decrease the expenses.
 Decrease the risk of failing in GMP.
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ORGANIZATION
DEPARTMENT DESIGNATION RESPONSIBILTY

R&D Executive officer To coordinate the entire validation process by scheduling

meetings and discussions with production, quality control and
quality assurance. Preparation of preliminary validation protocol,
master formula record.

Quality assurance Officer Preparation of validation protocol, monitoring the process,

compiling and analyzing data and test results and preparing the
final report. To review of validation documents

Production Officer To participate in performing the validation steps during

manufacturing processes. To assist in collection of data

Quality control Officer To test and report the test results

Quality assurance General manager To approve the process validation protocol

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CLASSIFICATION OF VALIDATION
METHODS

METHODS OF VALIDATION CAN BE CLASSIFIED AS

 PROCESS VALIDATION
 ANALYTICAL VALIDATION
 EQUIPMENT VALIDATION
 QUALIFICATION
 CLEANING VALIDATION
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VALIDATION MASTER PLAN

 A Validation Master Plan, also referred to as "VMP", outlines the principles involved in the
qualification of a facility, defining the areas and systems to be validated, and provides a
written program for achieving and maintaining a qualified facility. A VMP is the foundation
for the validation program and should include process validation, facility and utility
qualification and validation, equipment qualification, cleaning and computer validation.
 It is a key document in the GMP (Good manufacturing practice) regulated pharmaceutical
industry as it drives a structured approach to validation projects.
 Food and Drug Administration inspectors often look at VMPs during audits to see whether or
not a facility's validation strategy is well thought-out and organized. A VMP should have
logical reasoning for including or excluding every system associated with a validation project
based on a risk assessment.
MEMBERS OF VMP 11

 Validation manager(quality assurance department)

 Member from production
 Members of engineering
 Members from calibration lab
 Members from QC lab
 Members from maintenance
 Members from HVAC department
 Members from product development lab
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CONTENTS OF VMP
(FACTORS TO BE CONSIDERED)

 Introduction
 Methodology
 Qualification
 Personnel
 Schedule
 Preventative maintenance
 Change control
 Procedure
 Documentation
 Appendices
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INTRODUCTION 14

 This section is written as an introduction to the validation process and the

facility, and it is intended to set the scene
 The introduction of a VMP should include following details:
 a description of facility, its premises and equipment, and its purpose.
intension and scope of validation
 other relevant site policies and plans, like factory or corporate policy
statements on GMP,QA etc.
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METHODOLOGY

This section should address the predetermined requirements by identifying the

standards that are to be applied to the facility.
These are then used in the development of the acceptance criteria that are used to
judge the validation
It also involves planning and execution of documents such as, protocols, records,
reports, or other.
The standard will involve three elements:
 Regulatory and guidance documents
 National standards
 Company standards
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 The CFR 21 states “ Each person engaged in and each person responsible for
supervising the manufacture, processing, packaging or holding a drug product shall have
the education, training, and experience, or a combination thereof, to enable that person to
perform the assigned functions.”

 The VMP should lay down the principles for personnel requirements.It must address
the aspects like; experience of personnel (written biographies or CV), in-house training
reports, etc,.

 Documenting the training is essential and is a requisite of the GMPs.

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 Schedule:
 The work program is essential and should be prepared at an early stage.
 A good plan will contain all the necessary features which are to be considered during
execution of a plan and determines the control of the project.
 It ensures that all the personnel involved in the VMP are not only aware of the

engineering targets, but also the validation targets.

 Preventative maintenance:
 This is the responsibility of Site maintenance and Operation dept. This activity should
be performed during the design phase, and the documentation required should be, included
in the requisition.
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DOCUMENTATION

This section usually used to identify the documentation that should be

produced for the processing like;
• Engineering drawing
• Equipment supplier drawing and documents
• Factory acceptance documents
• IQ documents
• OQ documents
• PQ documents

Appendices:
The appendix is mostly used VMP to hold the information of type of
documents and formats that will be used in the execution stage
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CALIBRATION MASTER PLAN

“Automatic, mechanical, or electronic equipment or other types of equipment, including

computers, or related systems that will perform a function satisfactorily, maybe used in the
manufacture, processing, packing, and holding of a drug product. If such equipment is so
used, it shall be routinely calibrated, inspected, or checked according to a written program
designed to assure proper performance. Written records of those calibration checks and
inspections shall be maintained.”
-US Code of Federal Regulations, 21 CFR 211.68
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WHAT IS CALIBRATION??

The process of comparing the response of some instrument or system to a

standard instrument or system over some measurement range.

•To maintain the accuracy and precision of test equipment at all times.
•To ensure highest level of confidence in all measurement that affect materials
disposition decision, with unbroken chain of traceability to national standard.
•To determine whether the equipment is still fit for its intended purpose.
•It is based on the comparison of a primary standard or instrument of known
accuracy with another equipment (to be calibrated)
•It is used to detect, correlate, report or eliminate by adjustment of any variation in
the accuracy of the equipment being calibrated.
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WHAT IS CMP??

 Assigning responsibilities for equipment users, equipment managers, quality

assurance personnel, and calibration vendors to help ensure company-wide
consistency and regulation of your processes.
 Approving calibration vendors such that they are in compliance with the
guidelines of your Quality System.
 Identifying and labeling equipment.
 Processing investigations of out of tolerance conditions and other
calibration-related issues that may necessitate corrective action.
 Controlling and storing records, including calibration certificates, status
change forms, and calibration SOPs.
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WHY TO CALIBRATE??

 Components age and equipment undergoes changes in temperature or humidity or sustains mechanical
stress, performance degrades. This is called drift. Then test results become unreliable. While drift cannot
be eliminated, it can be detected and either corrected or compensated for through the process of
calibration.
 Properly calibrated equipment provides confidence that your products/services meet their specifications.
 Calibration : Optimizes resources
Ensures consistency
Ensures measurements and products are compatible with those made elsewhere
By making sure that your measurements are based on international standards, you promote acceptance of your
products/services/results
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REFERENCE STANDARD & MATERIAL

 Reference standard
It shall be calibrated by a body that can provide traceability. Such reference
standard of measurement held by the laboratory shall only be used for calibration.
It shall be calibrated before and after any adjustment
 Reference material
Where possible, it shall be traceable to SI units of measurement, or to certified
reference material. Internal reference material shall be checked as far as is
technically and economically practical
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CALIBRATION IDENTIFICATION

 Status of equipment calibration shall be available and affixed to the equipment

where applicable.
 Equipment identification shall bear the following information
 Name of equipment
 Serial number
 Date calibrated
 Status
 Schedule of next calibration and
 Initial/signature of the person who performed the calibration
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CALIBRATION PROCESS

 Calibration process must be managed and executed in a professional manner

 A particular place for all calibration operations to take place and keeping all
instruments for calibration
A separate room is preferred:
• Better environmental control
• Better protection against unauthorized handling or use of the calibration
equipment
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 The performance of all calibration operations is assigned as the clear

responsibility of just one person
 Calibration procedures, used for quality control functions, are controlled by the
international standards ISO 9000.
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MAINTENANCE OF RECORDS OF
CALIBRTION

 Records will be maintained for all the calibrations done

 It should be according to the cGMP
 The individual calibration history files will be prepared and maintained for each
instrument
 The records will be maintained and stored in the metrology or QA department
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LABELING

 All calibrated equipments are labelled or coded to indicate its status

 Labels should be design and made of material suitable to working environment
 Following declarations are to be made after calibration
 “calibrated’
 “calibration required”
 The label should contain
 Date of last calibration
 Date of recalibration
 Person responsible for calibration
 Calibration certificate number.
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CALIBRATION VALIDATION

Calibration assures accuracy of Validation provides proof of consistency

measurements. across all the processes, batches of
products or methods being used.
Calibration is a process that ensures that Validation is a documented process that
accuracy is maintained in the measurements provides assurance that a product, service
produced by your equipment. or system consistently provides results
within the acceptable criteria.
Calibration performance of any equipment There are no reference standards used in
is compared against a reference standard. validation.
It should be performed as per calibration It should be performed as per the
SOP. validation protocol.
You must periodically calibrate your There are no such requirements for
instruments. Identify if there is a ‘drift’ in validation. It should be performed when
the measurements and eliminate it through you make any change in the existing
calibration. system or when the revalidation period
has reached.
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REFERENCE

 Pharmaceutical process validation –By Ira R Berry

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