ICH and WHO guidelines for calibration and validation for equipments

1. ICH AND WHO GUIDELINES FOR
CALIBRATION AND VALIDATION OF
EQUIPMENTS
PRESENTED BY PRESENTED TO
NISHA . N PROF . H . S . KEERTHY
1ST M. PHARM DEPT.OF.PHARMACEUTICS
DEPT OF PHARMACEUTICS MALLIGE COLLEGE OF PHARMACY
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2. ICH GUIDELINES FOR CALIBRATION
AND VALIDATION OF EQUIPMENTS
CONTENTS
1) DESIGN AND CONSTRUCTION
2) CALIBRATION
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3. Design and Construction
1. Equipment used in the manufacture of intermediates and
APIs should be of appropriate design and adequate size,
and suitably located for its intended use, cleaning,
sanitization and maintenance.
2. Equipment should be constructed so that surfaces that
contact raw materials, intermediates, or APIs do not alter
the quality of the intermediates and APIs beyond the official
or other established specifications.
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4. 3. Production equipment should only be used within its
qualified operating range.
4. Major equipment (e.g., reactors, storage containers)
and permanently installed processing lines used during
the production of an intermediate or API should be
appropriately identified.
5. Any substances associated with the operation of
equipment, such as lubricants, heating fluids or coolants,
should not contact intermediates or APIs so as to alter
their quality beyond the official or other established
specifications.
6. Any deviations from this should be evaluated to ensure
that there are no detrimental effects upon the fitness for
purpose of the material. Wherever possible, food grade
lubricants and oils should be used.
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5. 7. Closed or contained equipment should be used
whenever appropriate. Where open equipment is used,
or equipment is opened, appropriate precautions
should be taken to minimize the risk of contamination.
8. A set of current drawings should be maintained for
equipment and critical installations (e.g.,
instrumentation and utility systems).
9. Equipment Maintenance and Cleaning.
10. Schedules and procedures (including assignment of
responsibility) should be established for the
preventative maintenance of equipment.
Written procedures should be established for cleaning of
equipment and its subsequentrelease for use in the
manufacture of intermediates and APIs.
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6. 11. Cleaning procedures should contain sufficient details to
enable operators to clean each type of equipment in a
reproducible and effective manner. These procedures
should include:
Assignment of responsibility for cleaning of equipment;
a) Cleaning schedules, including, where appropriate,
sanitizing schedules;
b) A complete description of the methods and
materials, including dilution of cleaningagents used to
clean equipment;
c) When appropriate, instructions for disassembling and
reassembling each article ofequipment to ensure proper
cleaning;
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7. d) Instructions for the removal or obliteration of
previous batch identification.
e) Instructions for the protection of clean
equipment from contamination prior to use.
f) Inspection of equipment for cleanliness
immediately before use, if practical; and
Establishing the maximum time that may elapse
between the completion of processingand
equipment cleaning, when appropriate.
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8. 12. Equipment and utensils should be cleaned, stored, and,
where appropriate, sanitized or sterilized to prevent
contamination or carry-over of a material that would alter
the quality of the intermediate or API beyond the official or
other established specifications.
13. Where equipment is assigned to continuous production or
campaign production of successive batches of the same
intermediate or API, equipment should be cleaned at
appropriate intervals to prevent build-up and carry-over of
contaminants.
14. Non-dedicated equipment should be cleaned between
production of different materials to prevent cross-
contamination.
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9. 15. Acceptance criteria for residues and the choice of
cleaning procedures and cleaning agents should be
defined and justified.
16. Equipment should be identified as to its contents and
its cleanliness status by appropriate means.
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10. Calibration
Control, weighing, measuring, monitoring and test
equipment that is critical for assuring the quality of
intermediates or APIs should be calibrated according
to written procedures and an established schedule.
1) Equipment calibrations should be performed using
standards traceable to certified standards, if existing.
2) Records of these calibrations should be maintained.
3) The current calibration status of critical equipment
should be known and verifiable.
4) Instruments that do not meet calibration criteria should
not be used.
5) Deviations from approved standards of calibration on
critical instruments should be investigated to
determine if these could have had an impact on the 10/26

11. quality of the intermediate(s) or API(s) manufactured
using this equipment since the last successful calibration.
6) GMP related computerized systems should be validated.
The depth and scope of validation depends on the diversity,
complexity and criticality of the computerized application.
7) Appropriate installation qualification and operational
qualification should demonstrate the suitability of
computer hardware and software to perform assigned
tasks.
8) Commercially available software that has been qualified
does not require the same level of testing. If an existing
system was not validated at time of installation, a
retrospective validation could be conducted if
appropriate documentation is available. 11/26

12. 9) Computerized systems should have sufficient controls to
prevent unauthorized access or changes to data. There
should be controls to prevent omissions in data (e.g.
system turned off and data not captured). There should be
a record of any data change made, the previous entry,
who made the change, and when the change was made.
10) Written procedures should be available for the operation
and maintenance of computerized systems.
11) Where critical data are being entered manually, there
should be an additional check on the accuracy of the
entry. This can be done by a second operator or by the
system itself.
12) Incidents related to computerized systems that could
affect the quality of intermediatesor APIs or the
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13. reliability of records or test results should be recorded
and investigated.
13) Changes to the computerized system should be made
according to a change procedure and should be formally
authorized, documented and tested. Records should be
kept of all changes, including modifications and
enhancements made to the hardware, software and any
other critical component of the system. These records
should demonstrate that the system is maintained in a
validated state.
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14. 14) If system breakdowns or failures would result in the
permanent loss of records, a back- up system should be
provided. A means of ensuring data protection should
be established for all computerized systems.
15) Data can be recorded by a second means in addition to
the computer system
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15. WHO GUIDELINES FOR CALIBRATION
AND VALIDATION OF EQUIPMENTS
CONTENTS
 Introduction.
 Instrument.
 Design qualification.
 Installation qualification.
 Operational qualification.
 Requalification.
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16. INTRODUCTION
Systems, utilities and equipment should be appropriately
designed, located, installed, operated, cleaned and maintained to
suit their intended purpose.
Products should be manufactured on qualified equipment to
ensure batch-to-batch consistency. These may include,
1. Computerized systems.
2. Water purification system.
3. Heating.
4. Ventilation.
5. Air conditioning systems
6. Production and quality control of equipment and instruments.
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17. Design qualification
Documented evidence that the premises, supporting systems,
utilities, equipment and processes have been designed in
accordance with the requirements of good manufacturing
practices.
Factory acceptance test
A test conducted at the vendor’s premises to verify that the
system, equipment or utility, as assembled or partially
assembled, meets expected specifications.
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18. Installation qualification.
The performance of tests to ensure that the installations (such as
machines, measuring devices, utilities and manufacturing areas)
used in a manufacturing process are appropriately selected and
correctly installed and operate in accordance with established
specifications.
Operational qualification
Documented verification that the system or subsystem performs
as intended over all anticipated operating ranges.
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19. Performance qualification
Documented verification that the equipment or system operates
consistently and gives reproducibility within defined specifications
and parameters for prolonged periods. (In the context of systems, the
term “process validation” may also be used.)
Site acceptance test
A test conducted at the site of use to verify that the system,
equipment or utility, as assembled or partially assembled meets
expected specifications.
System
A regulated pattern of interacting activities and techniques that are
united to form an organized whole.
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20. User requirement specifications
An authorized document that defines the requirements for use
of the system, equipment or utility in its intended production
environment.
Utility
A system consisting of one or more components to form a
structure designed to collectively operate, function or perform
and provide a service such as electricity, water, ventilation or
other.
The validation master plan, or other relevant document,
should specify the policy, organization, planning, scope and
stages applied in qualification for systems, utilities and
equipment and should cover, e.g. production, quality control and
engineering.
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21. Factory Acceptance Test and Site Acceptance
Test
Where a system, utility or equipment is assembled, or partially
assembled at a site other than that of the purchaser or end-user,
testing and verification should be done to ensure that the system,
utility or equipment is appropriate and ready for dispatch.
The checks and tests during assembly or partial assemble, should
be recorded.
Design Qualification
URS should be considered when deciding on the specific design of
a system, utility or equipment.
A suitable supplier should be selected for the appropriate system,
utility or equipment.
The supplier should be approved prior to purchasing the system,
utility or equipment.
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22. Installation Qualification
Systems, utilities and equipment should be correctly installed, in an
appropriate location and in accordance with an installation plan.
There should be documented evidence of the installation.
IQ should include identification and Measuring.
The calibration should be traceable to relevant national or international
standards. The execution of the protocol should be recorded in the IQ
report.
Operational qualification
Systems, utilities and equipment should operate correctly and their
operation should be verified in accordance with an OQ protocol.
Training of operators for the systems, utilities and equipment should
be provided and training records maintained.
All calibration, cleaning, maintenance, training and related tests and
results should be verified to be acceptable.
The outcome of the OQ should be recorded in the conclusion of the
report, before PQ is started. 22/26

23. Performance Qualification
Systems, utilities and equipment should consistently perform in
accordance with their design specifications.
The performance should be verified in accordance with a PQ
protocol. There should be records for the PQ (report) to indicate the
satisfactory performance over a period of time.
Manufacturers should justify the selected period over which PQ is
done. PQ should be done once OQ is successfully completed.
Requalification
Systems, utilities and equipment should be maintained in a qualified
state through the life of the system, utility or equipment.
Routine requalification of systems, utilities and equipment should be
considered based on the outcome of risk management principles
which include factors such as calibration, verification and
maintenance data and information.
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24. Qualification of “In-Use” Systems, Utilities and
Equipment
There should be data to support and verify the suitable design,
operation and performance of systems, utilities and equipment that
have been “in use” for a period of time and which have not been
subjected to IQ and or OQ.
These should include operating parameters and limits for critical
variables, calibration, maintenance and preventive maintenance,
SOPs and records.
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25. QUESTIONS
1) Explain WHO guidelines on calibration and validation of
equipments ?
2) Explain ICH guidelines for calibration and validation of
equipments ?
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