HEPA Filters for Pharma Applications

HEPA Filters for Pharma
Applications – Cleanrooms &
Safety Applications
Gordon Farquharson
June 2012
1
Air Filters at work
Images courtesy of CamfilFarr
2
How filters work
Sieving Effect
Straining
3
Filter Test Methods
4
Filter
Specifications
5
Some important filter considerations
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Correct pre-filters protect systems
& prolong life of final filters
HEPA filters are required in
cleanroom & safety ventilation
applications
Designs and installation must
allow for convenient & safe
filter testing
Make sure you know what filters
are installed in the system
6
HEPA Filter Standards
HEPA Filters are dealt with
in 4 basic ways.

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Filter Construction standards
Factory or manufacturer’s tests
In-situ testing of installations
Some application standards include HEPA Filter
specifications (e.g. EN 12469 for Biosafety Cabinets)
7
Filter Test Methods
MPPS = 0.2 
8
Some Test Equipment
Thermo-Pneumatic Aerosol Generator
9
Some Test Equipment
Laskin Nozzle
Cold Generator
10
Some Test Equipment
Aerosol Photometer
11
New Standards from
CEN TC 195 - Air Filtration 2

EN 1822-3 Testing
Planar Filter Medium
to determine the
MPPS -- Most
Penetrating Particle
size. The processes
of Interception,
Diffusion & Straining
give the following
classic curve.
Performance is
velocity dependent.
HEPA & ULPA Filters
v1
12
HEPA & ULPA Filters
EN 1822 - Factory Test
13
EN 1822 compared with
Eurovent 4/4 NaCl
Eurovent 4/4
EN 1822
Filter Class Efficiency % Filter Class Efficiency %
H 10
85
H 11
95
EU 10
95 - 99.9
H 12
99.5
EU 11
99.9 – 99.97
EU 12
99.97 – 99.99 H 13
99.95
EU 13
99.99– 99.999
H 14
99.995
EU 14
> 99.999
U 15
99.9995
U 16
99.99995
U 17
99.999995
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EN 1822-1 Filter Classifications
Local efficiency = 5x 0verall
H 10
H11
H12
H13
H14
U15
U16
U17
Overall Effic/Pen Local Effic/Pen
85 / 15 %
na / na
95 / 5
na / na
99.5 / 0.5
na / na
99.95 / 0.05
99.75 / 0.25 %
99.995 / 0.005
99.975 / 0.025
99.9995 / 0.0005
99.9975 / 0.0025
99.99995/0.00005
99.99975 / 0.00025
99.999995/0.000005 99.9999 / 0.0001
To avoid problems with In-situ test, always
specify a face scanned filter from the supplier !
15
Local & Overall Efficiency
H 14 example
@ MPPS
Local pen
< 0.025 %
Local & Overall
Pen % must pass
Local pen
< 0.025 %
Local pen
< 0.025 %
Overall penetration
< 0.005 % @ MPPS
16
Leak test In-situ
PAO test
Local pen
< 0.01 %
Local pen
< 0.01 %
Local pen
< 0.01 %
Overall penetration
< 0.001 or 0.003 % @ MPPS
17
Local & Overall Efficiency
H 14 example
18
How do we choose our HEPA filters ??
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From the requirements in a Cleanroom Standard or GMP
rule/guideline.
Because we have chosen a certain acceptance value for
the In-Situ leak test e.g. 0.001% or 0.01% .
Because we have calculated the efficiency of filter we need
from an evaluation of the particle challenge imposed upon
the filters.
Because the filter gives good Uni-Directional Flow.
Compliance with some other requirement
e.g. Corporate.
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Choosing the Right
http://www.phss.co.uk/
HEPA Filter
EU GMP Grade
A
Class
At Rest
14644-1 209E
 0.5 
ISO 5
100
M3.5
Class
In Operation
14644-1 209E
 0.5 
Air flow regime
and final filter
configuration
ISO 5
100
M3.5
UDAF
Terminal HEPA
filter
ISO 7
B
ISO 5
100
M3.5
10,000
M5.5
N-UDAF
Terminal HEPA
filter
C
ISO 7
10,000
M5.5
ISO 8
100,000
M6.5
N-UDAF
Terminal HEPA
filter
D
ISO 8
100,000
M6.5
Not defined
N-UDAF
In plant final filter
Final Filter
In situ test leak test
specification to
method
EN 1822
U15
H14
Face scan with
aerosol &
photometer
0.001 %
0.01 %
H14
Face scan with
aerosol &
photometer
0.01 %
H14
Face scan with
aerosol &
photometer
0.01 %
Volumetric overall
penetration.
0.01 %
H13
Refers to filter grades in accordance with EN 1822 ULPA , & HEPA
20
Test
acceptance
criteria =
stated %
The Installed HEPA Filter
21
Typical Aseptic Facility Design
(From ISPE HVAC GPG)
Outside air
treatment
AHU
22
In-Situ Testing General

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Select test method, aerosol, and acceptance
criteria
Determine challenge up-stream
Scan test final filter face for leaks
Determine acceptance or rejection
Carry out remedial work.
Agree before repairing filters. Have a clear policy.
ISO 14644-3 allows repair, subject to manufacturer’s
approved method.
I don’t know any manufacturers who encourage repairs.
Re-test
23
Testing is application specific
Filter testing in this Isolator
is a different problem from
the cleanroom.
24
Filter Systems for Potent,
Toxic, Biohazard
applications
25
Exposure Control Potent
Compound Control Bands
EH & S
Call the shots!
EXPOSURE CONTROL BAND
Band
OEL Range
Design
1
>1000 ug/m3
General Ventilation, Conventional open Equipment
with local exhaust (LEV)
2
50-1000 ug/m3
Semi-closed to closed materialo transfer
laminar flow/directionalized laminar flow
engineered LEV
3
20-50 ug/m3
Transfers using direct couplings % closed systems
selected use of unidirectionalized air flow booths
4
1-20 ug/m3
Totally enclosed processes: Transfers using direct
coupling barrier/isolator technology
5
<1 ug/m3
Isolator technology; remote operations fully
auotmated
26
Typical OSD Facility
Using Multiple Air handlers (From ISPE HVAC GPG)
27
BIBO (Bag-In, Bag-Out Housing
Fully Self contained system with fan, integrated
dampers & automatic scan section optional
Cover Panel
Access door for BT damper
Scan section
Hepa Section
Pre filter section
Air intake
levelling feet
28
29
Filter Leak Test Procedure!
30
31
Duct mounted double exhaust
housing
Safety ventilation systems - typical contemporary BSL-3
exhaust system
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32
High Total
Cost of
Ownership
Large
Each system
must be
specifically
oriented
Costly to test
Typical BSL-3 HEPA Filter
Exhaust System
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33
High Efficiency Particulate Air
(HEPA) Filter
Field system leak testing – manual
scanning
Potential Risk to
Certifier
 Requires lab shutdown
and system
decontamination
 Slow process

34
Field system leak testing – automated
scanning
Control Unit
35
Conclusions
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Be aware of the Different Standards
Understand the configuration
Specify filters correctly (including leak testing)
Install carefully
Test In-situ
Plan re-testing
Keep records
Thanks for your attention Questions?
37
PharmOut
Unit 20, 40 Montclair Avenue,
Glen Waverley,
Victoria,
Australia, 3150
Tel +61 (0) 3 8610 0169
Thanks for your attention
Slid
e 38
S
Y
S
CRITICAL
E
M
S
Gordon J Farquharson
Chair BSI LBI/030; Chair CEN TC243; Convenor ISO TC209 WG1.
c/o Critical Systems Ltd
www.critical-systems.co.uk
4, Greencroft, Guildford,
Surrey, GU1 2SY, UK.
tel +44 (0)1483 579926
mob +44 (0)7785 265 909
e-mail gj.farquharson@gmail.com & gjf@critical-systems.co.uk
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