Equipment Validation
Objective
At the end
of this session, student will be able to
• Discuss
the principles of qualification of equipment, with specific focus on:
• The
different stages of qualification
• Requalification
and
• Qualification
of “in use” equipment
• Discuss the requirements for equipment
• Selection
• Design
• Use
• Maintenance
Equipment
Principle
• Equipment must be
• Located
• Designed
• Constructed
• Adapted
• Maintained
• To suit the operations to be carried
out
• Equipment layout and design must
aim:
• to minimize risks of error
• to permit effective cleaning and
maintenance
• To avoid
• cross-contamination, dust and dirt
build-up
• any adverse effect on the quality of
products
• Equipment must be installed to:
• minimize risks of error
• minimize risks of contamination
Balances and Measuring
Equipment
• Appropriate range and precision
available
• In production and quality control
• Calibrated
• Scheduled basis
• Checks
• Records maintained
Production equipment
• Appropriate design
• Easily and thoroughly cleaned on a
scheduled basis
• procedures and records
• No hazard to the products
• Contact parts of suitable
non-reactive materials
• Non additive and not absorptive
• Defective equipment
• Removed, or labelled to prevent use
• Closed equipment used when possible
• Open equipment, or when equipment
opened, precautions taken to prevent contamination
• Non-dedicated equipment cleaned
according to validated cleaning procedures between different products
• Current drawings of critical
equipment and support systems maintained
Control laboratory equipment
• Equipment and instruments suitable
for the tests to be performed
• Defective equipment
• Removed
• Labelled
Washing, cleaning and drying
• Equipment used for washing and
drying – not the source of contamination
• Equipment design should promote easy
cleaning
• Cleaning on scheduled basis,
procedures and records
• Washing and cleaning
• Manual
• Automated (Clean in place (CIP),
Steam in place (SIP))
Basic Principles of GMP
Possible
Issues
• Poor design
• Lack of safety
• Poor quality finishes
• Lack of cleaning
• Lack of maintenance
• No usage log or record
• Use of inappropriate weighing
equipment
• Open-plan location of compressing
machines
Basic
Principles of GMP
• Remember to look at punches and dies
• Are there specifications for these?
• How are they cleaned, stored, issued
for use and returned to storage?
• Are they in a good condition and checked
at regular intervals?
Validation
General
• Qualification
policy for systems and equipment
• To
include instruments used in production and quality control
• New
systems and equipment: All stages of qualification applicable (DQ, IQ, OQ and
PQ)
• In
some cases: Not all stages of qualification may be required
e.g. electrical supply systems
•
Qualification
should be done in accordance with predetermined and approved qualification
protocols
•
The
results of the qualification should be recorded and reflected in qualification
reports
•
The
extent of the qualification should be based on the criticality of a system or
equipment, e.g.
Blenders, autoclaves
or computerized systems
• Qualification
should be done in accordance with predetermined and approved qualification
protocols
• The
results of the qualification should be recorded and reflected in qualification
reports
• The
extent of the qualification should be based on the criticality of a system or
equipment, e.g.
• Blenders,
autoclaves or computerized systems
Qualification and Validation
Definitions
• Validation
• Action
of proving, in accordance with the principles of GMP, that any procedure,
process, equipment, material, activity or system actually leads to the expected
results
• It is a process using documented evidence that
provides a high degree of assurance that a specific process will consistently
produce the predetermined outcome.
• Qualification
• Action
of proving that any premises, systems and items of equipment work correctly and
actually lead to the expected results
(Validation usually incorporates the concept of qualification)
• A
process of establishing confidence that the equipment is capable of consistently
operating within established limits and tolerances. Studies therefore done prior to use
• Qualification
– confirm
compliance with specified requirements or criteria (Do you have the right tool
for the job?)
–
Performed on one element or component of the process
to be validated
–
Conduct tests to establish if the component of a
process has the attributes to produce a specified outcome.
• Validation
– Proof. Document
that the process will consistently produce a predetermined outcome.
Validation
Stages of qualification
Design qualification
Installation qualification
Operational qualification
Performance qualification
General
Systems: Qualified before equipment
• Equipment:
Qualified before routine use
• Systems
and equipment: Periodic requalification, as well as requalification after change
• Certain
stages done by the supplier or a third party
• Maintain
the relevant documentation, e.g. standard operating procedures (SOPs),
specifications and acceptance criteria, certificates and manuals
Design qualification
• User
requirements should be considered when deciding on the specific design of a
system or equipment
• A
suitable supplier should be selected for the appropriate system or equipment (approved
vendor)
Installation qualification
• Verifies
that the correct equipment has been received and installed as per plan and
protocol. Also that it is complete and undamaged (parts, services, controls,
gauges and other components)
• Normally advised to prepare requirements for
calibration, maintenance and cleaning at this stage
• Verifies
that equipment has been properly installed and calibrated including connections
to utilities.
• Calibrate
the measuring, control and indicating devices against appropriate, traceable
national or international standards
• Documented
records for the installatio
• Installation
qualification report
• Indicate
satisfactory installation
• Include
details, e.g.
• The
supplier and manufacturer
• System
or equipment name, model and serial number
• Date
of installation
• Spare
parts, relevant procedures and certificates
Operational qualification
• Systems
and equipment should operate correctly – operation verified as in the
qualification protocol
• Verifies
that the equipment operates consistently within established limits and
tolerances over the defined operating ranges.
• Studies
on critical variable to include conditions encompassing upper and lower
operating limits and circumstances (i.e.
“worst case conditions”)
• Challenges
equipment functionally to verify compliance with manufacturer’s specifications
and end – user defined requirements. To include verification of operation of
all system elements, parts, services, controls, gauges and other components
• Documented
records (Operational qualification report)
• Finalize
and approve SOP (operation)
• Training
of operators provided – training records
• Systems
and equipment released for routine use after completion of operational
qualification, provided that:
• All
calibration, cleaning, maintenance, training and related tests and results were
found to be acceptable
How many 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
Qualification of Equipment
If one type and model of equipment is qualified, can it
be used in a different process without additional qualification?
• For
IQ document whether each equipment is installed correctly and operates
consistently according to established limits and tolerances. OQ should also be
performed for each different use of the equipment or system to document the
suitability for that use
• Not
be required for additional pieces of the same type/model of equipment when used
in the same process or for each piece of
the same type/model of equipment used in the same process, provided installation
qualification has been performed
Performance qualification
• Verifies
that the equipment performs according to design specifications and user defined
requirements in a reliable and reproducible manner under normal production
conditions
• Verified
in accordance with a performance qualification protocol
• Documented
records – performance qualification
report
• Show
satisfactory performance over a period of time i,e. carried out long enough to
prove that the equipment is under control and turns out product of specified
quality consistently.
• Manufacturers
to justify the selected period
Qualification Plan
• To
ensure that requirements are met and confirm by examination and collection of
objective evidence
• Challenges to equipment to be designed
• Re-create intended use
• Test, Test, Test
- Purpose
- Scope
- Equipment
Description - Operational
Specifications - Acceptance
Criteria - Testing
Results - Discrepancies/Corrective
Actions - Conclusions/Final
Report
“A qualification protocol / report”
• It reflects the minimum information
that should be included
• This is an example – and should be
used as such
• Specific formats need to be designed
for a specific system or piece of equipment
Worst Case Scenarios
• Conditions
that include upper and lower processing limits
• Circumstances
that present the highest chance of process or product failure relative to ideal
situations
• Identify
those conditions that are likely to be experienced during routine
manufacture/process
More Examples
The following case illustrates the importance of performing
adequate equipment qualification on each piece of processing equipment
• A
pharmaceutical firm used two blenders to produce a tablet. Both blenders
from same equipment manufacturer, same
model number and same design. Supplier told the drug manufacturer that the units
were “identical.” though one
was older. Manufacturer did not include the older blender as part of its
process validation.
More Examples
• Company
marketed about 100 batches of tablets using the old blender. Retention samples
showed some batches failed content
uniformity
• investigation
showed out of specification batches were from one of the two
“identical” blenders – the old
one. The older blender had a slightly smaller capacity and different
operational characteristics (RPMs) when run at the same settings as the newer
blender.
• Subsequently,
the firm recalled its total production of the product it made using the older
blender. The firm decided to qualify the old blender using production size lots.
Qualification of “Old”
Equipment
• What
about “old manufacturers” who have not performed DQ, or IQ for
existing, in-use systems and/or equipment?
• It
is not always possible to have all details for IQ or OQ for established equipment. The
manufacturer should however have data that verifies the operating parameters
and limits for the critical variables of the equipment. In addition,
calibration, cleaning, preventative maintenance, operating procedures and
operator training procedures for the use of the equipment should be documented
and used as SOPs ……. PIC/S
Qualification of “in-use” systems and equipment
• Data
to support and verify the suitable operation and performance of systems and
equipment
• Should
include operating parameters and limits for critical variables, calibration,
maintenance and preventive maintenance, standard operating procedures (SOPs)
and records
Risk assessment of operations or functions
Qualification flow Scheme
(extracted from CEFIC Guidance)
Example of Document Matrix
Requalification
• Required
for:
• Significant
change in batch size
• Change
in operating parameters
• Component
specifications have changed
• New
accessories or components are added to previously qualified equipment
• Process
changes that potentially impact product effectiveness or quality
Some Experiences
What if the results are not good?
• Study
report destroyed and manufacturer pretends it never happened So what should be
done?
• Document
the study, but don’t approve it
• Identify
and describe any corrective actions needed or any noteworthy observations or
deviations
• Start
another study using the findings and conclusions from the failed study
More experiences – poor qualification reports
• Specifications
not approved
• Failure
to provide clear, complete instructions in the protocol
• Instrument
calibration records or status not included
• Full
range of intended operating parameters not challenged
• Inadequate
sample sizes
• Atypical
data points
• Unexplained
deviations from protocol
• Inconsistencies
between final report and data collection/recording forms
WHO References
• Good
manufacturing practices (GMP):
guidelines on the validation of manufacturing processes
• Validation
of analytical procedures used in the examination of pharmaceutical materials
Summary
• Stages of qualification are
design qualification, installation qualification , performance
qualification etc
• Systems:
Qualified before equipment
• Equipment:
Qualified before routine use
• Systems
and equipment: Periodic requalification, as well as requalification after
change
• Certain
stages done by the supplier or a third party
• Maintain
the relevant documentation
• PQ verifies that the equipment performs
according to design specifications and user defined requirements in a reliable
and reproducible manner under normal production conditions