Supplementary Training Modules on

Good Manufacturing Practice

Heating, Ventilation and

Air-Conditioning (HVAC)

Part 3:
Commissioning, Qualification,
and maintenance

HVAC | Slide 1 of 28 May 2006

 HVAC

Objectives

 To understand key issues in

commissioning,

qualification and

maintenance of HVAC systems

8.

HVAC | Slide 2 of 28 May 2006

 HVAC
Documentation requirements to assist in
commissioning, qualification and maintenance
 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

HVAC | Slide 3 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 4 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 5 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 6 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 7 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 8 of 28 May 2006

 HVAC
 Design A C TIO N LIM IT A C TIO N LIM IT
conditions A LE R T LIM IT A LE R T LIM IT
and normal
operating
ranges set to
achievable
limits
D e s ig n C o n d itio n
 OOS results
recorded
N o r m a l O p e r a tin g R a n g e

O p e r a tin g R a n g e - V a lid a te d A c c e p ta n c e C r ite r ia

8.2.12 – 8.2.15

HVAC | Slide 9 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 10 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 11 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 12 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 13 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 14 of 28 May 2006

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

*Test procedure as per ISO 14644 8. Table 3

HVAC | Slide 15 of 28 May 2006

 HVAC
Recommended optional strategic tests
Test procedure* Maximum time Objective Test Parameter
and key aspects interval
Filter media and filter 12 months Verify filter integrity Filter leakage
seal integrity
Airflow direction and 12 months Verify absence of Containment leakage
pressure differential cross-contamination
Time taken maximum 12 months Verify clean-up time Recovery (time)
15 minutes

Airflow direction, 12 months Verify required airflow Airflow visualization

documented evidence patterns

*Test procedure as per ISO 14644 8. Table 3

HVAC | Slide 16 of 28 May 2006

 HVAC
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 | Slide 17 of 28 May 2006

 HVAC
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 See also ISO 14644

HVAC | Slide 18 of 28 May 2006

 HVAC

Cleanroom monitoring program (3)

Cleanrooms should be monitored for microorganisms and
particles
air

Example of a sampling point

HVAC | Slide 19 of 28 May 2006

 HVAC
Definition of Conditions

as built at rest in operation

air air air

HVAC | Slide 20 of 28 May 2006

 HVAC
Qualification – examples of aspects to consider in
qualification (OQ, PQ)
Uni-directional Turbulent / mixed
Test Description
airflow / LAF airflow

Differential pressure on filters 2 2

Room differential pressure N/A 2, 3 1 := As built (ideally used to perform IQ)

2 = At rest (ideally used to perform OQ)
Airflow velocity / uniformity 2, 3 Optional
3 = Operational (ideally used to perform PQ)
Airflow volume / rate 2 2

Parallelism 2 N/A

Airflow pattern 2 3

HVAC | Slide 21 of 28 May 2006

 HVAC
Qualification – examples of aspects to consider in
qualification (OQ, PQ)

Uni-directional Turbulent /
Test Description
airflow / LAF mixed airflow
Recovery time N/A 2 1 := As built (ideally used to perform IQ)
Room classification (airborne particle) 2 2,3 2 = At rest (ideally used to perform OQ)

Temperature, humidity N/A 2,3 3 = Operational (ideally used to perform PQ)

HVAC | Slide 22 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
8.3.1 – 8.3.5
– Qualification

HVAC | Slide 23 of 28 May 2006

 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)

HVAC | Slide 24 of 28 May 2006

 HVAC

Conclusion

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

HVAC | Slide 25 of 28 May 2006

 HVAC
Further proceedings

This series of explanations will now be followed by:

 Group discussion, with a simple exercise
 Short test

HVAC | Slide 26 of 28 May 2006

 HVAC
Group Session
S a m p lin g
Rooom S e rv ic e C o rrid o r
( c o n t a in s V a c u u m & R O w a t e r s u p p ly )
A ir S h o w e r

W a re h o u se
A ir L o c k 2 W e ig h in g T a b le t 1 T a b le t 2 L iq u id s M ix S o ftg e l C a p su le
P a c kin g
A / Lock 1

C le a n C o rrid o r
E m ergenc y
E x it

M a le F e m a le
2 S ta g e Change 2 Change 2
S te ril e e y e d ro p s p e rso n n e l P rim a ry & S e c o n d a ry
d isp e n sin g e n try fo r P a c ke d
P a c kin g
& a c e p tic fillin g e y e d ro p s G oods
A ir L o c k 3
Q u a ra n ti n e

M a le F e m a le
Change 1 Change 1
E q u ip m e n t W a sh A ir L o c k 4
S e rv i c e R o o m

HVAC | Slide 27 of 28 May 2006

 HVAC
Group Session – modified layout
20P a S a m p lin g
Rooom 0P a S e rv i c e C o rrid o r
30P a ( c o n t a in s V a c u u m & R O w a t e r s u p p ly )
A ir S h o w e r
20P a 30P a
10P a
W e ig h P o st
B o o th S ta g in g S o ftg e l C a p su le
W a re h o u se
20P a 30P a T a b le t 1 T a b le t 2 L iq u id s M ix P a c kin g
M AL 2 15P a 15P a 30P a
0P a
A ir L o c k
M AL1

15P a

30P a

C l e a n C o rri d o r
E m ergenc y
E x it

20P a 20P a
PAL
40P a M a le F e m a le 10P a
M AL 3 Change 2 Change 2 S e c o n d a ry P rim a ry
S te rile e y e d ro p s P a c kin g
40P a
P a c kin g
d isp e n sin g P a c ke d
& a sc e p tic fillin g G oods
Q u a ra n tin e 20P a 30P a
10P a 10P a
60P a
Change M a le F e m a le
15P a M AL 4
50P a Change 1 Change 1
E q u ip m e n t W a sh 50P a A ir L o c k 4
S e rv i c e R o o m 0P a
0P a

0P a
MAL = Material Air Lock
PAL = Personnel Air Lock
HVAC | Slide 28 of 28 May 2006