validation and calibration master plan

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PHARMACEUTICAL
VALIDATION
By
TANMAY PANIGRAHY
M.PHARM
RIPS, Berhampur

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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,
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
a systematic look at the pharmaceutical

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MERITS OFVALIDATION
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.

8. UNITS OF VALIDATION PLANNING AND
ORGANIZATION
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DEPARTMENT 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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METHODS OF VALIDATION CAN
PROCESS VALIDATION
ANALYTICAL VALIDATION
EQUIPMENT VALIDATION
QUALIFICATION
CLEANING VALIDATION
BE CLASSIFIED AS

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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.

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MEMBERS OF VMP
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
This section is written as an introduction to the validation process and
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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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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PERSONNEL
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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This section usually used to identify the documentation
produced for the processing like;
that should be
•Engineering drawing
•Equipment supplier drawing and
•Factory acceptance documents
•IQ documents
•OQ documents
•PQ documents
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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WHATIS 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 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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WHYTOCALIBRATE??
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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REFERENCESTANDARD & 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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CALIBRATIONIDENTIFICATION
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
“calibrated’ “calibration
required” The label
should contain Date of
last calibration
Date of recalibration
made after calibration
Person responsible for calibration
Calibration certificate number.

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You must periodically calibrate your
instruments. Identify if there is a ‘drift’in
the measurements and eliminate it through
calibration.
There are no such requirements for
validation. It should be performed when
you make any change in the existing
system or when the revalidation period
has reached.
CALIBRATION V
ALIDATION
Calibration assures accuracy of V
alidation provides proof of consistency
measurements. across all the processes, batches of
products or methods being used.
Calibration is a process that ensures that V
alidation 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.

31. ICH AND WHO GUIDELINES FOR CALIBRATION
AND VALIDATION OF EQUIPMENTS

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REFERENCE
Pharmaceutical process validation –By Ira R Berry