Transcript GMP Updated Training Modules

Supplementary Training Modules on
Good Manufacturing Practice
Heating,
Ventilation and AirConditioning
(HVAC)
WHO Technical Report Series,
No. 961, 2011. Annex 5
Part 4:
Commissioning,
qualification and
maintenance
Section 8
HVAC
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Slide 1 of 27
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HVAC
Objectives
 To understand key issues in
commissioning,
qualification and
maintenance of HVAC systems
8.
HVAC
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Slide 2 of 27
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HVAC
Documentation requirements to assist in
commissioning, qualification and maintenance
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Description of design, installation and functions
Specifications, requirements
Manuals
Operating procedures
Instructions for performance control, monitoring and records
Maintenance instructions and records
Training of personnel
― programme and records
Slide 3 of 27
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HVAC
Commissioning
Commissioning (is integrated in qualification) and includes:
 Setting up, balancing, adjustment and testing of entire HVAC
system
 It helps to ensure it meets URS and capacity
 Acceptable tolerances for parameters set before
commissioning
 Precursor to qualification
8.1.1, 8.1.4, 8.1.6
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Slide 4 of 27
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HVAC
Commissioning (2)
Records and data include:
 Installation records – documented evidence of measured
capacities of the system
 Acceptance criteria set for system parameters
 Training of personnel (e.g. operation and maintenance)
–
O&M manuals, schematic drawings, protocols, reports
8.1.2, 8.1.3,
8.1.5
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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.
 Risk-based approach for HVAC qualification
 See also full guidelines on "Validation" in WHO TRS No 937,
2005, Annex 4.
8.2.1
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HVAC
Qualification
 Described in a Validation Master Plan (VMP)
 Reflects the nature and extent, test procedures, 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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HVAC
Qualification
 Direct impact components and critical parameters should
be included
 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
8.2.6 - 8.2.11
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 Design
conditions
and normal
operating
ranges set to
achievable
limits
ACTION LIMIT
ALERT LIMIT
 OOL results
recorded and
investigated
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Slide 9 of 27
ALERT LIMIT
Design Condition
Normal Operating Range
Operating Range - Validated Acceptance Criteria
8.2.10 – 8.2.12
HVAC
ACTION LIMIT
2013
HVAC
Qualification – examples of aspects to consider
 DQ – Design of the system, URS
– (e.g. components, type of air treatment needed, materials
of construction)
 IQ – Verify installation
– e.g. relevant components, ducting, filters, controls,
monitors, sensors, etc.
– includes calibration where relevant
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HVAC
Qualification
Typical parameters to be included in qualification (based
on risk assessment):
 Temperature
 Relative humidity
 Supply, return and exhaust air quantities
 Room air change rates
 Room pressures (pressure differentials)
8.2.13
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HVAC
Qualification
Typical parameters to be included in qualification (based on
risk assessment) (2):
 Room air flow patterns
 Room clean-up rate
 Particulate matter, microbial matter (viable and non-viable)
 HEPA filter penetration tests
 Containment system velocity
 Warning/alarm systems
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8.2.13.
HVAC
Conduct of the tests:
 Time intervals and procedure to be defined by the
manufacturer - based on risk assessment (influenced by the
type of facility and level of protection)
 See also ISO 14644 for procedures
 Requalification, and change control
 Documents: system airflow schematics, room pressure
cascade drawings, zone concept drawings, air-handling
system allocation drawings, particle count mapping drawings
8.2.14 – 8.2.18
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HVAC
Qualification
 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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Schedule of tests to demonstrate continuing compliance
Test Parameter
Objective
Considerations
Test procedure*
and key aspects
Particle count test
Verifies cleanliness
Number of readings
and positions
Particle counter.
Readings and
positions
Air pressure
difference
Absence of crosscontamination
Continuous. Defined
limits
Measure pressure
difference
Airflow volume
Verify air change
rates
See ISO 14644
Measure supply and
return air, calculate
air change rate
Airflow velocity
Verify unidirectional
Velocity and
airflow and or
containment
containment condition
*Test procedure as per ISO 14644
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Slide 15 of 27
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Velocity
measurement
8. Table 3
HVAC
Recommended optional strategic tests
Test Parameter
Objective
Considerations
Test procedure*
and key aspects
Filter leakage
Verify filter integrity
For HEPA filters
Filter media and filter
seal integrity
Containment leakage
Verify absence of
cross-contamination
Containment, smoke
and air pressure
Airflow direction and
pressure differential
Recovery (time)
Verify clean-up time
Certain classes
Time taken maximum
20 minutes
Airflow visualization
Verify required airflow
patterns
Clean to dirty area,
uniformly. Video
Airflow direction,
documented evidence
*Test procedure as per ISO 14644
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8. Table 3
HVAC
Cleanroom monitoring program (1)
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Routine monitoring program as part of quality assurance
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Additional monitoring and triggers, e.g.
1. Shutdown
2. Replacement of filter elements
3. Maintenance of air-handling systems
4. Exceeding of established limits
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Cleanroom monitoring programme (2)
Particles and Microbiological
contaminants
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Number of points/locations for monitoring determined, specified,
documented in procedure and or protocol
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
See also ISO 14644
zone/class
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HVAC
Cleanrooms should be monitored for microorganisms and particles
Example of a sampling points
Sampling
Rooom
Service Corridor
(contains Vacuum & RO water supply)
Air Shower
A/ Lock1
Air Lock2
Warehouse
Weighing
Tablet 1
Tablet 2
Liquids Mix
Softgel Capsule
Packing
Clean Corridor
Emergency
Exit
Air Lock 3
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Slide 19 of 27
Male
Change 2
2013
Female
Change 2
Packed
Goods
Quarantine
Male
Change 1
Equipment Wash
HVAC
Sterile eyedrops
dispensing
& aceptic filling
2 Stage
personnel
entry for
eyedrops
Female
Change 1
Air Lock 4
Primary & Secondary
Packing
Service Room
HVAC
Qualification – examples of aspects to consider in
qualification (OQ, PQ)
Uni-directional
airflow / LAF
Test
Turbulent / mixed
airflow
Differential pressure on filters
2
2
Room differential pressure
N/A
2, 3
Airflow velocity / uniformity
2, 3
Optional
Description
1 := As built (ideally used to perform IQ)
2 = At rest (ideally used to perform OQ)
3 = Operational (ideally used to perform PQ)
Airflow volume / rate
2
2
Parallelism
2
N/A
Airflow pattern
2
3
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Slide 20 of 27
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Maintenance
 Procedure, programme and records for planned, preventative
maintenance
– e.g. cleaning of filters, calibration of devices
 Keep O&M manuals, drawings etc.
 Appropriate training for personnel
 Change of HEPA filters by suitably trained persons
 Impact of maintenance on:
– Product quality and Qualification
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8.3.1 – 8.3.6
HVAC
Premises may influence HVAC design / performance.
Therefore consider:
 Adequate airlocks, change rooms, passages
 Required pressure cascades
 Detailed diagrams available with pressure cascades, air
flow directions and flow routes for personnel and
materials should be prepared and maintained;
 Change room classification
9
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HVAC
Inspecting the air-handling system
 Verification of design documentation, including
 description of installation and functions
 specification of the requirements
 Operating procedures
 Maintenance instructions
 Maintenance records
 Training logs
 Environmental records
 Discussion on actions if OOS values
 On site verification (walking around the site)
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Slide 23 of 27
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Take home message. What is essential?
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Appropriate design of AHUs and HVAC system
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Correct components, and MOC
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Ensuring appropriate cleanliness of air, environmental conditions
(e.g. temperature and RH), and area classification to prevent
contamination and cross-contamination
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Qualification data to support claims
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Regular calibration, maintenance and cleaning
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HVAC
Conclusion
Air-handling systems:
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Play a major role in the quality of pharmaceuticals
Should be designed properly, by professionals
Should be treated as a critical system
Slide 25 of 27
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HVAC
Group Session
Sampling
Rooom
Service Corridor
(contains Vacuum & RO water supply)
Air Shower
A/ Lock1
Air Lock2
Warehouse
Weighing
Tablet 1
Tablet 2
Liquids Mix
Softgel Capsule
Packing
Clean Corridor
Emergency
Exit
Sterile eyedrops
dispensing
& aceptic filling
Air Lock 3
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Slide 26 of 27
Male
Change 2
2013
Female
Change 2
Packed
Goods
Quarantine
Male
Change 1
Equipment Wash
HVAC
2 Stage
personnel
entry for
eyedrops
Female
Change 1
Air Lock 4
Primary & Secondary
Packing
Service Room
HVAC
Group Session – modified layout
Sampling
Rooom
20Pa
0Pa
Service Corridor
(contains Vacuum & RO water supply)
30Pa
Air Shower
20Pa
10Pa
MAL 2
Warehouse
0Pa
Weigh
Booth
20Pa
30Pa
Post
Staging
Tablet 1
30Pa
Tablet 2
15Pa
Softgel Capsule
Packing
Liquids Mix
15Pa
30Pa
MAL1
Air Lock
15Pa
MAL = Material Air Lock
30Pa
Clean Corridor
PAL = Personnel Air Lock
Emergency
Exit
PAL
40Pa
MAL 3
Sterile eyedrops
dispensing
& asceptic filling
40Pa
20Pa
20Pa
Male
Change 2
Female
Change 2
10Pa
60Pa
15Pa
Equipment Wash
MAL 4
Change
50Pa
50Pa
10Pa
Male
Change 1
Female
Change 1
10Pa
Packed
Goods
Quarantine
Air Lock 4
0Pa
0Pa
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Slide 27 of 27
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Secondary
Packing
20Pa
Primary
Packing
30Pa
Service Room
0Pa