Tài liệu (Phần 3) | Hệ thống HVAC

1. 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

2. HVAC | Slide 2 of 28 May 2006
HVAC
Objectives
 To understand key issues in
commissioning,
qualification and
maintenance of HVAC systems
8.

3. 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

4. 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

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

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

7. 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

8. 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

9. 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
A C TIO N L IM IT
A L E R T L IM ITA L E R T L IM IT
A C TIO N L IM IT
O p e ra tin g R a n g e - V a lid a te d A c c e p ta n c e C rite ria
N o rm a l O p e ra tin g R a n g e
D e s ig n C o n d itio n

10. 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

11. 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

12. 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.

13. 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

14. 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

15. 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 Parameter Objective Maximum time
interval
Test procedure*
and key aspects
Particle count test Verifies cleanliness 6 months or 12
months depending on
Class
Particle counter.
Readings and
positions
Air pressure
difference
Absence of cross-
contamination
12 months Measure pressure
difference
Airflow volume Verify air change
rates
12 months Measure supply and
return air, calculate
air change rate
Airflow velocity Verify unidirectional
airflow and or
containment condition
12 months Velocity
measurement

16. HVAC | Slide 16 of 28 May 2006
HVAC
Recommended optional strategic tests
*Test procedure as per ISO 14644 8. Table 3
Test Parameter Objective Maximum time
interval
Test procedure*
and key aspects
Filter leakage Verify filter integrity 12 months Filter media and filter
seal integrity
Containment leakage Verify absence of
cross-contamination
12 months Airflow direction and
pressure differential
Recovery (time) Verify clean-up time 12 months Time taken maximum
15 minutes
Airflow visualization Verify required airflow
patterns
12 months Airflow direction,
documented evidence

17. 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

18. 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

19. 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

20. HVAC | Slide 20 of 28 May 2006
Definition of Conditions
air
as built
air air
at rest in operation
HVAC

21. 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

22. 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)

23. 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

24. 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

25. 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

26. 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

27. HVAC | Slide 27 of 28 May 2006
Group Session
S e r v i c e R o o m
W a re h o u s e
A/Lock1
AirLock2
A i r S h o w e r
S a m p l i n g
R o o o m S e rv i c e C o rr i d o r
(c o ntain s V a c uum & R O w ater s upply )
W e i g h i n g T a b l e t 1 T a b l e t 2 L i q u i d s M i x S o f t g e l C a p s u l e
P a c k i n g
E m ergenc y
E x it
C l e a n C o rr i d o r
E q u i p m e n t W a s h
A i r L o c k 3
S t e ri l e e y e d ro p s
d i s p e n s i n g
& a c e p t i c f i l l i n g
2 S t a g e
p e r s o n n e l
e n t ry f o r
e y e d ro p s
M a l e
C h a n g e 2
M a l e
C h a n g e 1
F e m a l e
C h a n g e 1
F e m a l e
C h a n g e 2
P a c k e d
G o o d s
Q u a ra n t i n e
A i r L o c k 4
P r i m a ry & S e c o n d a ry
P a c k i n g
HVAC

28. HVAC | Slide 28 of 28 May 2006
Group Session – modified layout
S e c o n d a r y
P a c k i n g
3 0 P a
0 P a
2 0 P a 3 0 P a
0 P a
0 P a
1 0 P a
1 0 P a 1 0 P a
2 0 P a2 0 P a
4 0 P a
5 0 P a
6 0 P a
5 0 P a
4 0 P a
1 5 P a
1 5 P a
P r i m a r y
P a c k i n g
C h a n g e
M A L 3
A i r L o c k
3 0 P a
P o s t
S t a g i n g
3 0 P a
3 0 P a
0 P a
1 5 P a1 5 P a
2 0 P a
2 0 P a
3 0 P a
2 0 P a
0 P a
1 0 P a
S e rv i c e R o o m
A i r L o c k 4
P a c k e d
G o o d s
Q u a ra n t i n e
F e m a l e
C h a n g e 2
F e m a l e
C h a n g e 1
M a l e
C h a n g e 1
M a l e
C h a n g e 2
P A L
S t e ri l e e y e d ro p s
d i s p e n s i n g
& a s c e p t i c f i l l i n g
M A L 4
E q u i p m e n t W a s h
C l e a n C o r ri d o r
E m ergenc y
E x it
S o f t g e l C a p s u l e
P a c k i n gL i q u i d s M i xT a b l e t 2T a b l e t 1
W e i g h
B o o t h
(c on tains V ac uum & R O w ate r s u pply )
S e rv i c e C o rri d o r
S a m p l i n g
R o o o m
A i r S h o w e r
MAL2
MAL1
W a re h o u s e
MAL = Material Air Lock
PAL = Personnel Air Lock
HVAC