1. Heating Ventilation and Air Conditioning (HVAC) – Part 3
Pharmaceutical Quality,
Good manufacturing Practice &
Bioequivalence
Kiev, Ukraine
3 - 7 October 2005
Maija Hietava
M.Sci.Pharm
Quality Assurance and Safety: Medicines, Medicines Policy and Standards, Health Technology and Pharmaceuticals Cluster
Tel: Fax:
World Health Organization

2. 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

3. Uni-directional / laminar displacement of dirty air
Air flow patterns (1)
Turbulent
dilution of dirty air
Uni-directional / laminar
displacement of dirty air
0,30 m/s

4. 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.

5. AHU Air flow patterns (3) Uni-directional Turbulent Prefilter
Main filter
Uni-directional
Turbulent 1 2 3
Annex 1, 17.3

6. Air flow patterns (4)
Workbench (vertical)
Cabin/ booth
Ceiling

7. Positioning of filters (1)
AHU mounted final filter
Filter in terminal position
HEPA Filter +
Production Room
Production Room
HEPA Filter

8. Positioning of filters (2)
Prefilter
AHU
Main filter
Ceiling
exhausts 2 3 1
Low level exhausts

9. Positioning of filters (3)
AHU
Prefilter
Final filter 2 1
Positioning of filters (3)

10. Air re-circulation The filtered air entering a production room can be
100% exhausted or
a proportion re-circulated
GMP aspect
economical reasons

11. Ventilation with 100% fresh air (no air re-circulation)
Washer (optional)
Exhaust Unit W
Central Air Handling Unit
Production Rooms

12. Ventilation with re-circulated air + make-up air
Exhaust Unit
Central Air Handling Unit
Return air

13. Definition of Conditions
air
as built
at rest
in operation

14. 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

15. 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
N/A
2, 3
Optional 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

16. Qualification (OQ, PQ) (2)
Test
Turbulent / mixed airflow
Description
Uni-directional airflow / LAF
Recovery time
Room classification (airborne particle)
Temperature, humidity
N/A 2
2,3
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

17. Microbiological validation
Definition of alert / action limits as a function of
cleanliness zone
Identification and marking of sampling points
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?”

18. Cleanroom monitoring program (1)
Cleanrooms should be monitored for micro-organisms
and particles
air
Sampling point

19. Cleanroom monitoring program (2)
Routine monitoring program as part of quality assurance
Additional monitoring and triggers
Shutdown
Replacement of filter elements
Maintenance of air handling systems
Exceeding of established limits
Annex 1, 17.37

20. Cleanroom maintenance program (1)

21. Cleanroom maintenance program (2)

22. Documentation requirements
Description of installation and functions
Specification of the requirements
Operating procedures
Instructions for performance control
Maintenance instructions and records
Maintenance records
Training of personnel (program and records)

23. Inspecting the air handling plant
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
Walking around the plant

24. Conclusion Air handling systems:
Play a major role in the quality of pharmaceuticals
Must be designed properly, by professionals
Must be treated as a critical system