Qualification of HVAC

systems Updated DEC 2015

Osama kamel farag
Egyptian engineering systems
www.ees9.com
Definitions
HVAC : Heat Ventilation and air conditioning
BMS : Building management system( A computerized system
that controls, monitors, and optimizes building services, this
may include environmental conditions, heating and cooling
systems, elevator systems, lighting, and security.
Qualification: (MHRA) Action of proving that any instrument
or equipment works correctly and actually leads to the expected
results.
Validation : Establishing documented evidence which provides
a high degree of assurance that a specific process will
consistently produce a product meeting its predetermined
specifications and quality attributes.
HVAC
Play a major role in the quality of pharmaceuticals
Critical system
Designed with special considrations
Different from commercial Hvac systems
HVAC Main components
Air handling system
Air handling units, Dehumidifier, Chillers ,….
Air distribution system
Ducts , VAV , grillers , HEPA filters,…
Building management system (BMS)
Sensors for temperature, pressure , humidity
computerized continues recording system
What is a Clean room?
A clean room is defined by ISO14644-1 as a room in
which the concentration of airborne particles is
controlled, and which is constructed and used in a
manner to minimize the introduction, generation, and
retention of particles inside the room and in which
other relevant parameters, e.g. temperature, humidity,
and pressure, are controlled as necessary.
Clean
As built
Room condition
At rest In operation

air air air
HVAC equipment qualification
 IQ Tests Installation
 Installation of components

 OQ Tests Installation
 Individual tests components (fans, coils, etc.)
 Functional tests sub-systems
 Verification control system

These tests confirme That the installation is working as a

whole and must be done before the room qualification
IQ Tests for an HVAC system
• Air Handling units with utility connections
• Ductwork
• Ventilation and Pressure Airflow Requirements
• Systems Design codes
• Insulation Material
• Damper and Air Volume Control Devices
• High Efficiency Particulate Air (HEPA) and Pre-filters
• Fire Detection System
• Direct Digital Control (DDC) System or Building
Management Systems (BMS)
OQ Tests for HVAC system
1. Review the HVAC IQ final report, instrument calibration,
and operation and maintenance procedures.
2. Review the testing and balancing final report.
3. Review the clean room testing and certification final report
(HEPA filter certification).
4. Verify HVAC control functions and alarms.
5. Verify Building Management System controls and
communication.
6. Verify pressure differentials and airflows between clean
rooms.
7. Complete shutdown and start-up tests to verify that the
HVAC systems return to normal conditions.
8. Verify Environmental Control Functions
Parameters to be qualified in a cleanroom
Room particle counts
Room clean-up rates
supply air quantities for all diffusers
return air or exhaust air quantities
Air changes (ACR) Air Change Rate per hour
Unidirectional air velocity
Room airflow patterns
Temperature
Humidity
Room pressure differentials
HEPA filter penetration
HEPA Filter Testing
HEPA filters are tested in two basic ways
Factory test
In situ testing of installation
GMP requires Max penetration≤ 0.01% using aerosol
generator + aerosol photometer
ISO 14644 requires Max penetration≤ 0.01% using
aerosol generator + aerosol photometer Or Particle
counter method
HEPA filter Testing Using Particle counter
HEPA Filter Test Using Aerosol Photometer
Generator Used To Inject Aerosol in the Filter Upstream
Distance not less than 25 of duct diameter (D)
In Case the distance is less than 25 D use special tool to
Ensure good mixing of Aerosol with Air
Measure the upstream concentration
it should be 20-80 µg/L
this will be 100% challenge
Full scan should be carried out
To filter face (media), Frame
and housing
Max allowable penetration 0.01%
Aerosol photometer specification
Equipment used to test HEPA filters
DOP hot smoke generator capable of generating
particles down to 0.3 microns in diameter.
 A photometer is used on the downstream side of the
filter to detect leaking particles. The photometer must
be able to detect particles down to 0.3 microns in
diameter.
Before starting the Dop Test
 The equipment is visually inspected for sources of
leakage such as cracked frames, holes or damage. The
filter must be properly installed and meet or exceed
the air flow rating of the equipment in which it is
installed.
 The DOP smoke generator must reach the proper
temperature to ensure that small range particles are
generated.
ISO 14644-1 Classification of Cleanrooms
EU GMP Annex-1Particle limits

For cleanroom certification testing of Grade A

zones, a minimum sample volume of 1m3 should be
taken per sample location.
Measurement of air cleanliness
Equipment
Air particle counter
with specific flow rate
For ISO 5 clean room we need to
sample 1 m3 of
Using 100 LPM
particle counter will do the job
10 minutes/ location
Particle counters flow rate
Hand held particle counters
0.1 CFM (2.8 LPM)
Suitable for ISO 7,8
Portable particle counters
1 CFM (28 LPM)
2 CFM (50 LPM)
3 CFM ( 75 LPM)
4 CFM ( 100 LPM)
Suitable for ISO 5,6,7,8
No of channels 2,3,4,6,8
Channel Size suitable for pharma
industries 0.3 ,0.5,5 micron
Old standard 2009
New standard 2015
According to Published table
Calculation for number of points
Example of sampling locations
Particle counters used in clean room
Calibrated according to ISO 21501 requirement's
Able to return to zero point in all channels using absolute
filter
Minimum channel size 0.3 Micron (its counting efficiency
50 % (± 20 %) for particles close to the minimum
detectable size)
For the next channel size 0.5 micron measuring efficiency
100 % (± 10 %) for particles 1.5-2 times larger than the
minimum detectable size
Zero count test ≈ ≤ 1 count / 5 minutes
Comparison Annex-1 to ISO 14644-1
How to calculate sample volume per
location

Vs : sample volume in liter

Cn, m : no of particle in the class and size
Example :
ISO 5 Clean room
limit for size 0.5 micron 3520 particl
Vs= (20/3520)*1000 = 5.6 Liter
Limit for size 5 micron 29 particle
Vs= (29/29)*1000 =690 liter
Particle count calculations
Average sample data values at each position
Normalize the average to number of particles per cubic meter
Compare normalized value to the target class limit;
normalized value at each and every sample point must be less
than the limit for the given size and target room classification
If the number of points sampled is more than 1 but less than
10,
then the UCL factor must be applied:
 Calculate the standard deviation
 Use Student’s T-factor from tables

 Calculate UCL

 Compare to classification limit; UCL must not exceed the

applicable limit
ISO 14644-1 the minimum sample volumes for each of the Grade
areas in liters

•The volume sampled at each location shall be at least 2

liters, with a minimum sample time of 1 minute.

•When Vs is very large, the time required for sampling can be

substantial. By using the sequential sampling procedure (see
annex F), both the require sample volume and time required
to obtain samples may be reduced
Sequential Sampling

In sequential sampling the running total of the

particles counted is compared with an expected count
limit that is a function of the amount of sampling
done. Sequential sampling typically requires less
sampling than any single sampling plan having the
same probability of false acceptance and false
rejection.
sequential sampling boundaries
iso14644 Annex F

the boundaries of the sequential sampling plan that has been designed for use
in
this standard. The observed number of counts, C, is plotted against the
expected number of counts, E, for air, which is precisely at the class limit. A
full single sample corresponds to E = 20.
Therefore, if the expected particle counts should be 10 and only 5 have been
measured, the sampling can stop, the location declared a pass, and
sampling can be started at the next location.
Results obtained from air particle counter
Counts for different channels
Counts normalized /Ft3 or per m3
Pass or fail results according to iso14644-1
Results documented in a clean room
test report
Area drawings
Copy of calibration certificate
of used particle counter
ISO 14644-1 calculations
Average sample data values at each position
2.Normalize the average to number of particles per cubic meter
3.Compare normalized value to the target class limit; normalized
value at each and every sample point must be less than the limit
for the given size and target room classification
If the number of points sampled is more than 1 but less than 10,
then the UCL factor must be applied:
 Calculate the standard deviation
 Use Student’s T-factor from tables

 Calculate UCL

 Compare to classification limit; UCL must not exceed the applicable

limit
Schedule of testing to demonstrate
particle count compliance
Schedule for additional tests for all classes
(1)
Schedule for clean room testing- continue
Cleanliness recovery test (clean up rate)
Recovery rate (also referred to as clean up rate) can be
determined for different area classes. The test can give
a good indication of the time it takes to clean a room
after it had been contaminated with particles. The test
is often performed as part of the initial qualification of
a system or area. ISO14644 does not recommend this
test for ISO 8 areas.
Air quantities measurements in cleanroom
Flowhood with flowmeter
measures airflow rate from an area
over which there can be
variations in airflow, providing an
integrated air volume from that area.
The total airflow is collected and
concentrated so that the velocity at
the measurement point represents the
cross-sectional average velocity from
the total area.
Iso 14644-Flowhood specification
Air Change rate
Flowhood with flowmeter
specification as per iso14644-2
Airflow patterns

Unidirectional airflow
may be either vertical or horizontal
ISO Class 5 and cleaner in operation
Non-unidirectional airflow
typical for cleanrooms of ISO Class 6 and less clean in
operation.
Mixed-airflow cleanrooms combine both
unidirectional and non-unidirectional airflow in the
same room.
Unidirectional airflow laf unit
Multi-directional flow clean room
Vertical unidirectional cleanroom
Visualization of air flow pattern
Equipmen
Clean room fog generator to comply with ISO 14644 - 3
Annex B7,
Mapping air flows using high purity water fog generators or
similar.
performing a smoke study
 The cleanroom fogger (Figure 1) that generates a fog or
smoke from water vapor using water for injection (WFI)
or deionized water is recommended. Methods for
generating the water vapor fog include megasonic
vaporization, steam (liquid nitrogen), and dry ice.
These units are commercially available.
video camera, trained manufacturing personnel, and
trained smoke study personnel are also required for
conducting these studies. Training is essential for these
studies. Strict adherence to procedures is mandatory
Example

Unidirectional flow good example No movement for smok

 Unidirectional air velocity measurment

 the laminar flow velocity (0.36-0.54 m/s) at working position

Air Speed measuring Devices
Hot wire Anemometer
Range (0.1-1 m/s)
Resolution (0.05m/s)
Can measure low speed suitable for
LAF units air speed measurements
Mini fan anemometer
Fan anemometer
Range (0.2-10 m/s)
Resolution (0.1m/s)
Air Speed
Room Differential pressure
Room DP layout
Differential pressure between rooms
 measuring with a calibrated manometer the differential pressure
existing between the inside of a clean room and the surrounding
areas as defined in the specifications.
 This determination should be made under various operational
conditions such as day mode, night mode, opening of doors, etc. to
identify also situations when the pressure differential cannot be
met and as a consequence
the product may be at risk.
Electronic manometer specification as per
ISO 14644-3
Temperature and humidity
Temperature level and uniformity test
 The purpose is to demonstrate the capability of the clean room / HVAC
system to maintain air temperature wihin the specified limits and over a
certain period of time.
 The result of this test can also be used to support qualification of the
location of fixed installed temperature monitoring devices.
Humidity level and uniformity test
 The purpose of this test is to demonstrate the capability of the
clean room (HVAC system with (de)humidification units) to
maintain air humidity levels within the specified limits and
over a certain period of time.
 The result of these tests can also be used to support
qualification of the location of fixed installed humidity monitoring
devices.
Temperature and humidity devices
Hand held instrument
Data logger
Thanks


Questions?