EQUIPMENT VALIDATION
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CONTENT
Introduction
Validation Study Phases
Master Validation Protocol
Dissolution Apparatus Validation
Conclusion
References
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INTRODUCTION
A validation programme involves various components in
pharmaceutical organisation related to process, equipment and
product.
It is a regulatory requirement for pharmaceutical companies to perform
Instrument Validation on all new instruments.
Instrument Validation requires detailed knowledge of the
instrumentation system being validated and is therefore usually
performed by the company supplying the instrument.
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EQUIPMENT VALIDATION
Definition (US-FDA):- Validation is the establishment of
documentary evidence which provide a high degree
assurance of specified process will consistently produce the
product meeting with predetermined specification and
quality attributes.
Validation studies are performed for analytical equipment,
tests, facility systems such as air, water, steam, the
manufacturing, cleaning, sterilization processes
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CYCLE OF VALIDATION
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VALIDATION STUDY PHASES
Phase 1:
Pre-Validation Phase (Qualification Phase)
Phase 2:
Process Validation Phase (Process Qualification phase)
Phase 3:
Validation Maintenance Phase
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VALIDATION PLAN
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PHASE-1(QUALIFICATION)
DESIGN QUALIFICATION:
“A documented review of the design, at an appropriate stage or
stages in the project, for conformance to operational and regulatory
expectations.”
Specification of requirements for facilities, plants and
equipment, mainly in connection with purchase/modification
of equipment.
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DQ REVIEW DOCUMENTS
User Requirement Specification (URS)
Functional Specification (FS)
Tender Specifications and Drawings
Vendor Quality procedures and documents
Purchase Specification
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INSTALLATION QUALIFICATION
IQ verifies that the equipment has been installed in accordance
with the manufacturer’s recommendation in a proper manner
and that all of the devices are placed in an environment suitable
for their intended purpose.
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COMPUTER AND SOFTWARE IQ
Software Requirements and Specifications should be clear, written
down, and approved by the appropriate personnel prior to creating
the software package.
Software Installation should be recorded, when made, so that the
proper model numbers, serial numbers ,installation date, etc
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Phase-2
(process qualification phase)
OPERATIONAL QUALIFICATION
The documented action of demonstrating that process equipment and
ancillary systems work correctly and operate consistently In
accordance with established specifications.
Operation Qualification (OQ) for testing the equipment in the selected
user environment to ensure that it meets the previously defined
functional and performance specifications.
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How may runs are to be performed during Operational
Qualification (OQ) testing?
Guidelines stress the importance of equipment qualification simulating
actual production conditions, including 'worst case' situations and that
"tests and challenges should be repeated a sufficient number of times to
assure reliable and meaningful results."
"three consecutive batches" is recommended for process validation rather
than for equipment qualification. No specific number of "runs" for
equipment qualification, but multiple tests to simulate actual operating
ranges and to establish consistency are expected
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PERFOMANCE QUALIFICATION
Assurance that the process continues to comply with
established requirements.
Performance Qualification (PQ) for testing that the
system consistently performs as intended for the
selected application.
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Performance Qualification
Purpose- To define testing requirements in a product/
process/performance/qualification/validation protocol.
Principle- Performance qualification validation testing plan
are usually process or product specific but will include the
following background and result for the plan, testing
method used, and a predetermined and general and/or
specific acceptance criteria.
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RE-VALIDATION
Re-validation is required when the operating
equipment or system has been changed in some way.
It is carried out when:
Major mechanical equipment has been replaced
Computer systems have been replaced
New products have to be run on the system.
Critical items have been replaced or repaired.
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RETRO-VALIDATIONS
Retrospective validation must be done on equipment that records have
either been lost or validation was not provided for in the initial life of
the machine. Retrospective validations get more difficult the older
the machine.
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PHASE-3
(VALIDATION MAINTENANCE PHASE)
It is the maintenance of the validation which has been
already
established.
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MASTER VALIDATION PROTOCOL
The Master Validation Protocol (MVP) is the outline of the
validation for a facility.
MVP :
Identifies which items are subjects to validation.
Defines the nature and extent of testing expected to be done on each
item.
Outlines the test procedures and protocols to be followed to
accomplish validation.
Describes functional responsibilities and requirements to document
the work carried out and the results obtained.
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Installation Qualification
Installation qualification consists of documented
verification that all key aspects of the dissolution
apparatus are in working condition and have been
properly installed in accordance with manufacturer’s
specifications in the proper operating environment.
Calibration
The installation qualification should document that
specific devices contained within the dissolution
apparatus (e.g., speed, time, and temperature displays)
have been calibrated to traceable standards.
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INSTALLATION QUALIFICATION-
Environmental Conditions
Computerized System
Equipment Information
Preventive maintenance
SOP
Utilities
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DISSOLUTION APPARATUS
VALIDATION
Dissolution is defined as the process by which a known
amount of drug substance goes into solution per unit of
time under standardized conditions.
The primary goal of dissolution testing is to be used as a
qualitative tool to provide measurements of the
bioavailability of a drug as well as to demonstrate
bioequivalence from batch-to-batch.
Validation is achieved by performing a series of validation
activities; for a dissolution apparatus, validation is obtained
through installation qualification and operational
qualification.
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DISSOLUTION APPARATUS
• Apparatus 1
• Vessel: cylindrical, 160-210 mm height, inside diameter 98-
106 mm, nominal capacity is 1000 mL; sides are flanged at
the top. Shaft: positioned so that its axis is not more than 2
mm at any point from the vertical axis of the vessel and
rotates smoothly and without significant wobble.
Materials of Construction: Shaft and basket components
are stainless steel, type 316 or equivalent. Basket position:
the distance between the inside bottom of the vessel and the
basket is maintained at 25 +/- 2 mm during the test.
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DISSOLUTION APPARATUS
Apparatus 2 • Vessel: cylindrical, 160-210 mm height, inside
diameter 98-106 mm, nominal capacity is 1000 mL; sides are
flanged at the top. Shaft: positioned so that its axis is not more
than 2 mm at any point from the vertical axis of the vessel and
rotates smoothly and without significant wobble.
• Materials of Construction: Shaft and blade are a single entity
that may be coated with a suitable inert coating.
Blade position: the distance between the inside bottom of the
vessel and the blade is maintained at 25 +/- 2 mm during the test.
The blade passes through the diameter of the shaft so that the
bottom of the blade is flush with the bottom of the shaft 24
OPERATIONAL QUALIFICATION:
Operational Qualification Operational Qualification
consists of documented evidence that the equipment
operates as intended and is capable of consistent
operation within established specifications.
The operational qualification of a dissolution apparatus
should include the following verifications:
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• Temperature Distribution Study
A temperature distribution study should be conducted
during the operational qualification. The study should
include temperature mapping of each vessel contained
within the dissolution apparatus. Temperature should
be mapped using a data system for a minimum time
that is based on the monograph or 1 hour, whichever is
greater. The temperature must remain at 37°C ± 0.5°C;
Rotation Speed Study
A rotation speed study should be conducted during the
operational qualification. The study should include a
measurement of the speed of the shaft rotation for each
vessel contained within the dissolution apparatus.
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SYSTEM SUITABILITY
A system suitability test using USP calibrators should be
conducted during operational qualification testing. The
procedure for dissolution and sampling is outlined in the
Certificates supplied with each USP Calibrator tablet for
each apparatus. The calibrators used for the test are
disintegrating tablets (Prednisone) and non disintegrating
tablets (Salicylic Acid). The test is successful if the percent
of drug released at 30 minutes falls within a pre-established
range.
The ranges for each combination of apparatus and
calibrators at 50 or 100 RPM are established by the USP and
are different for each lot of calibrators.
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Performance Qualification
In Performance qualification different types of
dosage form are used.
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CONCLUSION
Validation provide the good quality product and the equipment .
Validation give the surety that equipment having the good
qualification like design, operation, installation, and performance
qualification which have pre-determined.
Validation data should be generated for the all types of the product
and the equipment to demonstrate the adequacy of the
manufacturing
process
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REFERENCES
1. Potdar Manohar A. “Pharmaceutical quality assurance” 2 nd Edition, Nirali
Prakashan, p-8.1-8.7
2. Nash Robert A. “Pharmaceutical Process Validation”3 rd Edition, Marcel Dekker Inc,
p-442
3. Cole Graham C. ‘Pharmaceutical Production Facilities” 2 nd Edition, CRC Press, p-
199
4. Despautz Joseph F. “Automation And Validation Of Information In Pharmaceutical
Processing” Vol-90, Marcel Dekker Inc, p-221
5. Berry And Harpaz “ Validation Of Active Pharmaceutical Ingredient”2 nd Edition,
CRC Press, p-429
6. Sharon M.Averell Frost, “ Introduction to the Validation of a Dissolution
Apparatus.”p-19.
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