HVAC | Slide 1 of 28 May 2006 Heating, Ventilation and Air-Conditioning (HVAC) Part 3: Commissioning, Qualification, and maintenance Supplementary Training Modules on Good Manufacturing Practice
GMP Updated Training ModulesHeating, Ventilation and
Air-Conditioning (HVAC)
Part 3:
HVAC
Objectives
commissioning,
Specifications, requirements
Maintenance instructions and records
HVAC
HVAC
Commissioning
Precursor to qualification
Includes setting up, balancing, adjustment and testing of entire
HVAC system to ensure it meets requirements in URS and
capacity
Acceptable tolerances for parameters
8.1 Commissioning
8.1.1 Commissioning should include the setting up, balancing,
adjustment
and testing of the entire HVAC system, to ensure that it meets all
the
requirements, as specifi ed in the user requirement specifi cation
(URS), and
capacities as specifi ed by the designer or developer.
8.1.2 The installation records of the system should provide
documented
evidence of all measured capacities of the system.
8.1.3 The data should include items such as the design and
measurement
fi gures for airfl ows, water fl ows, system pressures and
electrical amperages.
These should be contained in the operating and maintenance
manuals
(O & M manuals).
8.1.4 Acceptable tolerances for all system parameters should be
specifi ed
prior to commencing the physical installation.
8.1.5 Training should be provided to personnel after installation
of the
system, and should include operation and maintenance.
HVAC | Slide * of 28 May 2006
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Installation records – documented evidence of measure capacities of
the system
Data: Design and measurement for, e.g. airflow, system
pressures
O&M manuals, schematic drawings, protocols, reports
8.1.2, 8.1.3, 8.1.6
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8.1.3 The data should include items such as the design and
measurement
fi gures for airfl ows, water fl ows, system pressures and
electrical amperages.
These should be contained in the operating and maintenance
manuals
(O & M manuals).
8.1.4 Acceptable tolerances for all system parameters should be
specifi ed
prior to commencing the physical installation.
8.1.5 Training should be provided to personnel after installation
of the
system, and should include operation and maintenance.
8.1.6 O & M manuals, schematic drawings, protocols and reports
should
be maintained as reference documents for any future changes and
upgrades
to the system.
HVAC
Qualification
Validation is an extensive exercise
Qualification of the HVAC system is one component in the overall
approach that covers premises, systems/utilities, equipment,
processes, etc.
See also full guidelines on "Validation" in WHO TRS No 937, 2005,
Annex 4.
Risk-based approach for HVAC qualification
8.2.1
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8.2 Qualifi cation
8.2.1 Validation is a many-faceted and extensive activity and is
beyond
the scope of these guidelines. Qualifi cation and validation
guidelines are
included in: Expert Committee on Specifi cations for Pharmaceutical
Preparations.
Fortieth report. Geneva, World Health Organization, 2005 (WHO
Technical Report Series, No. 937), Annex 4 (see also Fig.
28).
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Described in a Validation Master Plan (VMP)
VMP to include the nature and extent of tests, and protocols
DQ, IQ, OQ, and PQ
Risk analysis to determine critical and non-critical parameters,
components, subsystems and controls
8.2.2 - 8.2.5
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8.2.2 The qualifi cation of the HVAC system should be described in
a validation
master plan (VMP).
8.2.3 It should defi ne the nature and extent of testing and the
test procedures
and protocols to be followed.
8.2.4 Stages of the qualifi cation of the HVAC system should
include DQ,
IQ, OQ and PQ.
8.2.5 Critical and non-critical parameters should be determined by
means
of a risk analysis for all HVAC installation components, subsystems
and
controls.
HVAC
Non-critical systems and components are subjected to Good
Engineering Practices (GEP)
Acceptance criteria and limits defined in design stage
Design conditions, normal operating ranges, operating ranges, alert
and action limits
8.2.5 - 8.2.11
8.2.5 Critical and non-critical parameters should be determined by
means
of a risk analysis for all HVAC installation components, subsystems
and
controls.
8.2.6 Any parameter that may affect the quality of the
pharmaceutical
product, or a direct impact component, should be considered a
critical
parameter.
8.2.7 All critical parameters should be included in the qualifi
cation process.
Note: A realistic approach to differentiating between critical and
noncritical
parameters is required, to avoid making the validation
process
unnecessarily complex.
Example:
• The humidity of the room where the product is exposed should be
considered
a critical parameter when a humidity-sensitive product is
being
manufactured. The humidity sensors and the humidity monitoring
system
should, therefore, be qualifi ed. The heat transfer system,
chemical drier or
steam humidifi er, which is producing the humidity controlled air,
is further
removed from the product and may not require operational qualifi
cation.
Figure 28
Qualifi cation is a part of validation
Equip 1 Equip 2 Equip 3 Equip 4 Equip 5 Equip 6
QUALIFICATION
VALIDATION
System operating ranges
• A room cleanliness classifi cation is a critical parameter and,
therefore,
the room air change rates and HEPA fi lters should be critical
parameters
and require qualifi cation. Items such as the fan generating the
airfl ow
and the primary and secondary fi lters are non-critical parameters,
and
may not require operational qualifi cation.
8.2.8 Non-critical systems and components should be subject to GEP
and
may not necessarily require qualifi cation.
8.2.9 A change control procedure should be followed when changes
are
planned to the direct impact HVAC system, its components and
controls
that may affect critical parameters.
8.2.10 Acceptance criteria and limits should be defi ned during the
design
stage.
8.2.11 The manufacturer should defi ne design conditions, normal
operating
ranges, operating ranges, and alert and action limits.
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Design conditions and normal operating ranges set to achievable
limits
OOS results recorded
HVAC
(e.g. components, type of air treatment needed, materials of
construction)
IQ – Verify installation
includes calibration where relevant
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Qualification (4)
Typical parameters to be included in qualification (based on risk
assessment):
Temperature
Room air change rates
Room pressures (pressure differentials)
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8.2.17 For a pharmaceutical facility, based on a risk assessment,
some of
the typical HVAC system parameters that should be qualifi ed may
include:
— temperature
— room air change rates
— room pressures (pressure differentials)
— room airfl ow patterns
— unidirectional fl ow velocities
— room particle counts
— room clean-up rates
— operation of de-dusting
HVAC
Qualification (5)
Typical parameters to be included in qualification (based on risk
assessment) (2):
Room clean-up rate
HEPA filter penetration tests
HVAC
Time intervals and procedure to be defined by the
manufacturer
Influenced by the type of facility and level of protection
See also ISO 14644 for methods of testing
Requalification, and change control
8.2.18 – 8.2.20, 8.2.9
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8.2.18 The maximum time interval between tests should be defi ned
by the
manufacturer. The type of facility under test and the product level
of protection
should be considered.
Note: Table 3 gives intervals for reference purposes only. The
actual test periods
may be more frequent or less frequent, depending on the product and
process.
8.2.19 Periodic requalifi cation of parameters should be done at
regular
intervals, e.g. annually.
8.2.20 Requalifi cation should also be done when any change, which
could
affect system performance, takes place.
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Tests performed according to protocols and procedures for the
tests
Results recorded and presented in report (source data kept)
Traceability, e.g. devices and standards used, calibration records;
and conditions specified
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*Test procedure as per ISO 14644
8. Table 3
Particle count test
Particle counter. Readings and positions
Air pressure difference
Absence of cross-contamination
Airflow velocity
12 months
Velocity measurement
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8. Table 3
Filter leakage
Containment leakage
Recovery (time)
Airflow visualization
Cleanroom monitoring program (1)
Additional monitoring and triggers, e.g.
1. Shutdown
HVAC
Cleanroom monitoring programme (2)
Particles and Microbiological contaminants
Sufficient time for exposure, and suitable sample size
Identification and marking of sampling points
Definition of transport, storage, and incubation conditions
Results to reflect the procedure/protocol followed
Define alert and action limits as a function of cleanliness
zone/class
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air
Cleanroom monitoring program (3)
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Definition of Conditions
Qualification – examples of aspects to consider in qualification
(OQ, PQ)
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Test
3 = Operational (ideally used to perform PQ)
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This slide shows a series of tests to be carried out during
qualification.
There are different tests for the turbulent and for the
uni-directional air flows.
The differential pressure on filters is an indication of the
clogging of the filters: with the charging of dust on the filters,
the differential pressure will increase.
In order to keep the volume of air constant, the fan speed may
increase, with the following consequences:
Damage to filters, and passage of unfiltered air
Particles and micro-organismes will be “pushed” through the filter
units.
(Inspectors should check whether pressure differential manometers
are installed on the AHUs. Without this means of monitoring the
filters, the system could go out of control causing contamination
problems.)
Airflow patterns are interesting to visualize (smoke tests), as
zones without proper flushing can be easily identified.
It is also important to monitor air flow velocities for each HEPA
filter according to a program of established intervals because
significant reductions in velocity can increase the possibility of
contamination, and changes in velocity can affect the laminarity of
the airflow.
Airflow patterns should be tested for turbulence, as these can
interfere with the flushing action of the air.
HVAC | Slide * of 28 May 2006
Qualification – examples of aspects to consider in qualification
(OQ, PQ)
HVAC
Test
3 = Operational (ideally used to perform PQ)
World Health Organization
The recovery time (clean-up time) is also an important parameter to
be determined. Once doors have been opened and people have been
entering a room, the original conditions have been disturbed and,
for a short while, before recovering, the room does not always
correspond to the laid down parameters.
It is important to know how long this period is. There are no
regulations laid down as to how long this clean-up time should be.
However, the generally accepted time to clean-up from one cleanroom
classification to the next higher classification, should be less
than 15 minutes.
It should also be remembered that a room is to be qualified “in
operation” when it has a certain number of people in it. After
qualification, the number of people in that room, as challenged
during qualification, cannot be exceeded.
Temperature and humidity can also be important (comfort in clean
areas, stability of effervescent products, etc.)
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Maintenance
e.g. cleaning of filters, calibration of devices
Appropriate training for personnel
Impact of maintenance on:
8.3.1 There should be a planned preventive maintenance
programme,
procedures and records for the HVAC system. Records should be
kept.
8.3.2 Maintenance personnel should receive appropriate
training.
82
8.3.3 HEPA fi lters should be changed either by a specialist or a
trained
person.
8.3.4 Any maintenance activity should be assessed critically to
determine
any impact on product quality including possible
contamination.
8.3.5 Maintenance activities should normally be scheduled to take
place
outside production hours, and any system stoppage should be
assessed with
a view to the possible need for requalifi cation of an area as a
result of an
interruption of the service.
Verification of design documentation, including
description of installation and functions
specification of the requirements
On site verification (walking around the site)
Inspecting the air-handling system
Air-handling systems:
Should be designed properly, by professionals
Should be treated as a critical system
Conclusion
HVAC
This series of explanations will now be followed by:
Group discussion, with a simple exercise
Short test
Further proceedings
Group Session
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The diagram, which is given in handout 3-3-26, shows a layout of a
small pharmaceutical plant for non-sterile tablets, liquids and
soft-gel capsules, as well as aseptically filled eye-drops.
The group session participants should indicate on the diagram the
required cleanroom classes, room pressures (in Pa), as well as any
architectural changes which they think necessary.
(This layout is not ideal, but as many different types of
operations have been incorporated in the facility as possible, so
that different concepts can be addressed.)
(Note to trainer: The next handout, 3-3-27, giving suggested
modifications, should not be distributed until after the group
discussion has taken place.)
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Group Session – modified layout
MAL = Material Air Lock
PAL = Personnel Air Lock
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This slide indicates the proposed additions, and can be displayed
after the group session discussions have taken place. See handout
3-3-27.
ACTION LIMIT
Normal Operating Range
Packing
Emergency
Exit
Service Corridor