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
HVAC | Slide 2 of 28 May 2006
HVAC
Objectives

To understand key issues in
commissioning,
qualification and
maintenance of HVAC systems
8.
HVAC | Slide 3 of 28 May 2006
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
Documentation requirements to assist in
commissioning, qualification and maintenance
HVAC
HVAC | Slide 4 of 28 May 2006
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
Training of personnel
8.1.1, 8.1.4, 8.1.5
HVAC | Slide 5 of 28 May 2006
HVAC
Commissioning (2)
Records and data maintained include:
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
HVAC | Slide 6 of 28 May 2006
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
HVAC | Slide 7 of 28 May 2006
HVAC
Qualification (2)
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
HVAC | Slide 8 of 28 May 2006
HVAC
Qualification (3)
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
8.2.5 - 8.2.11
HVAC | Slide 9 of 28 May 2006
HVAC
Design
conditions
and normal
operating
ranges set to
achievable
limits
OOS results
recorded
8.2.12 8.2.15
ACTION LIMIT
ALERT LIMIT ALERT LIMIT
ACTION LIMIT
Operating Range - Validated Acceptance Criteria
Normal Operating Range
Design Condition
HVAC | Slide 10 of 28 May 2006
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
HVAC | Slide 11 of 28 May 2006
HVAC
Qualification (4)
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)
8.2.17
HVAC | Slide 12 of 28 May 2006
HVAC
Qualification (5)
Typical parameters to be included in qualification (based on
risk assessment) (2):
Room clean-up rate
Particulate matter, microbial matter (viable and non-viable)
HEPA filter penetration tests
Containment system velocity
Warning/alarm systems
8.2.17.
HVAC | Slide 13 of 28 May 2006
HVAC
Qualification (6)
Conduct of the tests:
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
HVAC | Slide 14 of 28 May 2006
HVAC
Qualification (7)
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
HVAC | Slide 15 of 28 May 2006
HVAC
Schedule of tests to demonstrate continuing compliance








*Test procedure as per ISO 14644


8. Table 3
Test procedure*
and key aspects
Maximum time
interval
Objective Test Parameter
Particle counter.
Readings and
positions
6 months or 12
months depending on
Class
Verifies cleanliness Particle count test
Measure pressure
difference
12 months Absence of cross-
contamination
Air pressure
difference
Measure supply and
return air, calculate
air change rate
12 months Verify air change
rates
Airflow volume
Velocity
measurement
12 months Verify unidirectional
airflow and or
containment condition
Airflow velocity
HVAC | Slide 16 of 28 May 2006
HVAC
Recommended optional strategic tests






*Test procedure as per ISO 14644

8. Table 3
Test procedure*
and key aspects
Maximum time
interval
Objective Test Parameter
Filter media and filter
seal integrity
12 months Verify filter integrity Filter leakage
Airflow direction and
pressure differential
12 months Verify absence of
cross-contamination
Containment leakage
Time taken maximum
15 minutes
12 months Verify clean-up time Recovery (time)
Airflow direction,
documented evidence
12 months Verify required airflow
patterns
Airflow visualization
HVAC | Slide 17 of 28 May 2006
Cleanroom monitoring program (1)
Routine monitoring program as part of quality assurance
Additional monitoring and triggers, e.g.
1. Shutdown
2. Replacement of filter elements
3. Maintenance of air-handling systems
4. Exceeding of established limits


HVAC
HVAC | Slide 18 of 28 May 2006
Cleanroom monitoring programme (2)
Particles and Microbiological
contaminants
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
zone/class
HVAC
See also ISO 14644
HVAC | Slide 19 of 28 May 2006
air
Example of a sampling point
Cleanroom monitoring program (3)
Cleanrooms should be monitored for microorganisms and
particles
HVAC
HVAC | Slide 20 of 28 May 2006
Definition of Conditions
air
as built
air
air
at rest in operation
HVAC
HVAC | Slide 21 of 28 May 2006
Qualification examples of aspects to consider in
qualification (OQ, PQ)
Test
Differential pressure on filters
Turbulent / mixed
airflow
Description
Uni-directional
airflow / LAF
Room differential pressure
Airflow velocity / uniformity
Airflow volume / rate
Parallelism
Airflow pattern
2 2
N/A 2, 3
2, 3 Optional
2 2
2 N/A
2 3
1 := As built (ideally used to perform IQ)
2 = At rest (ideally used to perform OQ)
3 = Operational (ideally used to perform PQ)


HVAC
HVAC | Slide 22 of 28 May 2006
Test
Turbulent /
mixed airflow
Description
Uni-directional
airflow / LAF
Recovery time
Room classification (airborne
particle)
Temperature, humidity
N/A 2
2 2,3
N/A 2,3
1 := As built (ideally used to perform IQ)
2 = At rest (ideally used to perform OQ)
3 = Operational (ideally used to perform PQ)
HVAC
Qualification examples of aspects to consider in
qualification (OQ, PQ)
HVAC | Slide 23 of 28 May 2006
HVAC
Maintenance
Procedure, programme and records for planned, preventative
maintenance
e.g. cleaning of filters, calibration of devices
Appropriate training for personnel
Change of HEPA filters by suitably trained persons
Impact of maintenance on:
Product quality
Qualification
8.3.1 8.3.5
HVAC | Slide 24 of 28 May 2006
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)
Inspecting the air-handling system
HVAC
HVAC | Slide 25 of 28 May 2006
Air-handling systems:
Play a major role in the quality of pharmaceuticals
Should be designed properly, by professionals
Should be treated as a critical system

Conclusion
HVAC
HVAC | Slide 26 of 28 May 2006
This series of explanations will now be followed by:
Group discussion, with a simple exercise
Short test

Further proceedings
HVAC
HVAC | Slide 27 of 28 May 2006


Group Session
Servi ce Room
Warehouse
A
/

L
o
c
k

1
A
i
r

L
o
c
k

2
Ai r Shower
Sampl i ng
Rooom
Servi ce Corri dor
(contains Vacuum & RO water supply)
Wei ghi ng Tabl et 1 Tabl et 2 Li qui ds Mi x Softgel Capsul e
Packi ng
Emergency
Exit
Cl ean Corri dor
Equi pment Wash
Ai r Lock 3
Steri l e eyedrops
di spensi ng
& acepti c fi l l i ng
2 Stage
personnel
entry for
eyedrops
Mal e
Change 2
Mal e
Change 1
Femal e
Change 1
Femal e
Change 2
Packed
Goods
Quaranti ne
Ai r Lock 4
Pri mary & Secondary
Packi ng
HVAC
HVAC | Slide 28 of 28 May 2006


Group Session modified layout
Secondary
Packi ng
30Pa
0Pa
20Pa 30Pa
0Pa
0Pa
10Pa
10Pa 10Pa
20Pa 20Pa
40Pa
50Pa
60Pa
50Pa
40Pa
15Pa
15Pa
Pri mary
Packi ng
Change
MAL 3
Ai r Lock
30Pa
Post
Stagi ng
30Pa
30Pa
0Pa
15Pa 15Pa
20Pa
20Pa
30Pa
20Pa
0Pa
10Pa
Servi ce Room
Ai r Lock 4
Packed
Goods
Quaranti ne
Femal e
Change 2
Femal e
Change 1
Mal e
Change 1
Mal e
Change 2
PAL
Steri l e eyedrops
di spensi ng
& ascepti c fi l l i ng
MAL 4
Equi pment Wash
Cl ean Corri dor
Emergency
Exit
Softgel Capsul e
Packi ng
Li qui ds Mi x Tabl et 2 Tabl et 1
Wei gh
Booth
(contains Vacuum & RO water supply)
Servi ce Corri dor
Sampl i ng
Rooom
Ai r Shower
M
A
L

2
M
A
L
1
Warehouse
MAL = Material Air Lock
PAL = Personnel Air Lock
HVAC