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Heating

Ventilation and
Air Conditioning (HVAC)

Part 3: Design, qualification
and maintenance
Air Handling Systems
Supplementary Training Modules
on GMP
Module 3, Part 3: Qualification and maintenance Slide 1 of 27 WHO - EDM
Module 3, Part 3: Design, qualification and maintenance Slide 2 of 27 WHO - EDM
Air Handling Systems
Characteristics of air handling systems

In the following slides, we will study alternatives in air
handling systems

Turbulent or uni-directional airflows
Filter position
Air re-circulation vs fresh air
Return air systems (positions)
Overpressure requirements


Module 3, Part 3: Design, qualification and maintenance Slide 3 of 27 WHO - EDM
Air Handling Systems
Uni-directional / laminar
displacement of dirty air
Turbulent
dilution of dirty air
0,30 m/s
Annex 1, 17.3
Air flow patterns (1)
Module 3, Part 3: Design, qualification and maintenance Slide 4 of 27 WHO - EDM
Air Handling Systems
Air flow patterns (2)
Filtered air entering a production room or covering a
process can be
turbulent
uni-directional (laminar)
GMP aspect
economical aspect

New technologies: barrier technology/isolator
technology.

Annex 1, 17.3, 17.4
Module 3, Part 3: Design, qualification and maintenance Slide 5 of 27 WHO - EDM
Air Handling Systems
Prefilter
Air flow patterns (3)
AHU
Main filter
Uni-directional
Turbulent Turbulent
1
2 3
Annex 1, 17.3
Module 3, Part 3: Design, qualification and maintenance Slide 6 of 27 WHO - EDM
Air Handling Systems
Workbench (vertical) Cabin/ booth Ceiling
Air flow patterns (4)
Module 3, Part 3: Design, qualification and maintenance Slide 7 of 27 WHO - EDM
Air Handling Systems


Positioning of filters (1)
Filter in terminal position AHU mounted final filter
Production Room
+
Production Room
HEPA Filter
HEPA Filter
Module 3, Part 3: Design, qualification and maintenance Slide 8 of 27 WHO - EDM
Air Handling Systems
Prefilter
AHU
Main filter
1
2 3
Low level exhausts
Ceiling
exhausts
Positioning of filters (2)
Module 3, Part 3: Design, qualification and maintenance Slide 9 of 27 WHO - EDM
Air Handling Systems
AHU
Prefilter
Final filter
2 1
Positioning of filters (3)
Module 3, Part 3: Design, qualification and maintenance Slide 10 of 27 WHO - EDM
Air Handling Systems
Air re-circulation
The filtered air entering a production room can be

100% exhausted or
a proportion re-circulated

GMP aspect
economical reasons



Annex 1, 15.10, 17.24
Module 3, Part 3: Design, qualification and maintenance Slide 11 of 27 WHO - EDM
Air Handling Systems
Ventilation with 100% fresh air (no air re-circulation)
Annex 1, 17.24
W
Washer (optional)
Central Air Handling Unit
Production Rooms
Exhaust Unit
Module 3, Part 3: Design, qualification and maintenance Slide 12 of 27 WHO - EDM
Air Handling Systems
Ventilation with re-circulated air + make-up air
Central Air Handling Unit
Return air
Exhaust Unit
Module 3, Part 3: Design, qualification and maintenance Slide 13 of 27 WHO - EDM
Air Handling Systems
Definition of Conditions
air
as built
air
air
at rest in operation
Module 3, Part 3: Design, qualification and maintenance Slide 14 of 27 WHO - EDM
Air Handling Systems
Qualification / Validation issues
A good design is essential, but it has to be complemented by:
Qualification of air handling systems
Process validation
Maintenance and periodic re-qualification
Adequate documentation
Module 3, Part 3: Design, qualification and maintenance Slide 15 of 27 WHO - EDM
Air Handling Systems
Qualification (OQ, PQ) (1)
Test
Differential pressure on filters
Turbulent / mixed
airflow
Description
Uni-directional
airflow / LAF
Room differential pressure
Airflow velocity / uniformity
Airflow volume / rate
Parallelism
Air flow 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)


IQ tests are not mentioned on this slide
Annex 1, 17. 4
Module 3, Part 3: Design, qualification and maintenance Slide 16 of 27 WHO - EDM
Air Handling Systems
Qualification (OQ, PQ) (2)
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)
Annex 1, 17. 4
IQ tests are not mentioned on this slide
Module 3, Part 3: Design, qualification and maintenance Slide 17 of 27 WHO - EDM
Air Handling Systems
ACTION LIMIT
ALERT LIMIT ALERT LIMIT
ACTION LIMIT
Operating Range - Validated Acceptance Criteria
Normal Operating Range
Design Condition
Microbiological validation
1. Definition of alert / action limits as a function of
cleanliness zone
1. Identification and marking of sampling points
2. Definition of transport, storage, and incubation conditions





Ask the question:
What are the alert
and action Limits and
what procedures are
followed if these
points are exceeded?

Module 3, Part 3: Design, qualification and maintenance Slide 18 of 27 WHO - EDM
Air Handling Systems
air
Sampling point
Cleanroom monitoring program (1)
Cleanrooms should be monitored for micro-organisms
and particles
Module 3, Part 3: Design, qualification and maintenance Slide 19 of 27 WHO - EDM
Air Handling Systems
Cleanroom monitoring program (2)
Routine monitoring program as part of quality assurance
Additional monitoring and triggers
1. Shutdown
2. Replacement of filter elements
3. Maintenance of air handling systems
4. Exceeding of established limits

Annex 1, 17.37
Module 3, Part 3: Design, qualification and maintenance Slide 20 of 27 WHO - EDM
Air Handling Systems
Cleanroom maintenance program (1)
Schedule of Tests to Demonstrate Continuing Compliance
Test Parameter
Class Maximum Time
Interval
Test Procedure
A, B
<= ISO 5
6 Months ISO 14644 -1 Annex A
Particle Count Test
C, D
> ISO 5
12 Months ISO 14644 -1 Annex A
Air Pressure Difference
All Classes 12 Months ISO 14644 -1 Annex B5
Air Flow
All Classes 12 Months ISO 14644 -1 Annex B4
Module 3, Part 3: Design, qualification and maintenance Slide 21 of 27 WHO - EDM
Air Handling Systems
Cleanroom maintenance program (2)
Schedule of Additional Optional Tests
Test Parameter
Class Maximum Time
Interval
Test Procedure
Installed Filter Leakage
All Classes 24 Months ISO 14644-1 Annex B6
Containment Leakage
All Classes 24 Months ISO 14644-1 Annex B4
Recovery
All Classes 24 Months ISO 14644-1 Annex B13
Air Flow Visualisation
All Classes 24 Months ISO 14644-1 Annex B7
Module 3, Part 3: Design, qualification and maintenance Slide 22 of 27 WHO - EDM
Air Handling Systems
1. Description of installation and functions
2. Specification of the requirements
3. Operating procedures
4. Instructions for performance control
5. Maintenance instructions and records
6. Maintenance records
7. Training of personnel (program and records)
Documentation requirements
Module 3, Part 3: Design, qualification and maintenance Slide 23 of 27 WHO - EDM
Air Handling Systems
1. Verification of design documentation, including
description of installation and functions
specification of the requirements
2. Operating procedures
3. Maintenance instructions
4. Maintenance records
5. Training logs
6. Environmental records
7. Discussion on actions if OOS values
8. Walking around the plant
Inspecting the air handling plant
Module 3, Part 3: Design, qualification and maintenance Slide 24 of 27 WHO - EDM
Air Handling Systems
Air handling systems:
1. Play a major role in the quality of pharmaceuticals
2. Must be designed properly, by professionals
3. Must be treated as a critical system

Conclusion
Module 3, Part 3: Design, qualification and maintenance Slide 25 of 27 WHO - EDM
Air Handling Systems
This series of explanations will now be followed by:
Group discussion, with a simple exercise
Short test

Further proceedings
Module 3, Part 3: Design, qualification and maintenance Slide 26 of 27 WHO - EDM
Air Handling Systems

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
Module 3, Part 3: Design, qualification and maintenance Slide 27 of 27 WHO - EDM
Air Handling Systems

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