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"HEPA filtration - Specification; Leak testing;

Bleed-through; and other nightmares."

Gordon Farquharson, Bovis Lend Lease Technology, May 2008

Gordon Farquharson
I am an Engineer with >30 years experience
of Pharma/Life Science
Principal Consultant with the leading
International Firm Bovis Lend Lease.
Very active in associations including ISPE.
I have been writing the ISO Cleanroom
Standards -- Chair of CEN TC 243 &
Convenor of WG1 in ISO TC 209.
I am the author of WHOs draft
Pharmaceutical Water GMP.
Active is ISPEs Baseline writing

Profile - Bovis Lend Lease
Services provided range from strategic and management consultancy
through to major project implementation, providing a single point of
Strategic Studies, Business Planning, User Brief Development, Feasibility Studies,
Equipment (Selection Specification and Procurement), production and Process
Improvements, Manufacturing Outsourcing, Potent Product handling.
Regulatory Compliance and Validation Services
Regulatory Strategy Consultancy. Compliance with Safety Health and
Environmental regulations. GLP and GMP audits. Preparation and implementation
of IQ, OQ and RD protocols. Development of ISO 9000 Quality Systems.
Equipment, Environmental, Laboratory, Computer and Cleaning Validation.
Information Technology and Automation Systems
IT Consultancy, Automation System Consultancy, Software System Design,
Integration and Implementation, Process Automation and Software Validation.
Design, Engineering and Construction Management
The design and realisation of Research, Development, Production and
Administration Facilities. This includes concept through to detail design, cost
engineering, project management, management of construction, equipment
installation, commissioning, facility Start-Up and ongoing operation.

Is the following familiar?

New HEPA fail the in-situ leak test.

Bleed-through occurs across full face
of filter >0.01% penetration.
Interesting discussions with test-house
and filter supplier.
High temperature filters fail leak tests
and shed particles.
QA investigations - challenging.

HEPA & ULPA Filters
Scope of Presentation
Selection efficiency & velocity
In Situ Testing

Standards & Regulatory
Requirements for HEPA & ULPA

HEPA Filter Standards
HEPA Filters are tested in 2 basic ways.
Factory or manufacturers tests
Europe + exported product EN 1822
In-situ testing of installations
GMP expectations (aerosol/photometer), leaks
0.01% irrespective of filter spec H14 or
U15 to pass test.
BSI PD 6609:2007 (aerosol/photometer)
BS EN ISO 14644-3 (aerosol/photometer +
particle counter method)

Some Other Test Standards

EN 12463:1999
for Microbiological Safety Cabinets
Replacement for parts of BS5726:1992 produced
by CEN TC233-Biotechnology.
KI-Discus & spore containment tests are
specified for type testing. In the UK version Ki-
Discus is specified for In-Situ testing.
Aerosol/Photometer filter test:-
Filter class not specified
Scan test penetration 0.003%
Mineral oil & suitable generator.
MMD of aerosol is defined.
Alternatives can be used e.g. DOP, DEHS, or
Parafin oil.
MPPS here
Filter Performance ~ 0.2

Efficiency MPPS shifts with
Velocity Change

Double the
loose an
order of 0.0007% @ 0.2
in filter

0.005% @ 0.15

Filter Test Methods Test
aerosols are different MMD

EN 1822-4 Scan testing the filter
element - Manufacturer
A face scan test to determine the extent of local
leaks. The local Efficiency or Penetration at
Integrate results to give the overall Efficiency or
Penetration %age.
Automatic scanning particle counter.
Record the values
The test DOES NOT require scanning of the
frame and seals of the filter. Some suppliers have
decided to do this as part of their testing.

EN 1822-4 Scan testing the filter
element - Manufacturer
HEPA & ULPA Filters
EN 1822

EN 1822-1 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
H 15 99.9995
H 16 99.99995
H 17 99.999995

Note: H14 can be less efficient than old EU 14s

EN 1822-1 Filter Classifications
Local efficiency = 5x 0verall
Overall Effic/Pen Scan - Local Effic/Pen
H 10 85 / 15 % na / na
H11 95 / 5 na / na
H12 99.5 / 0.5 na / na
H13 99.95 / 0.05 optional 99.75 / 0.25 %
H14 99.995 / 0.005 99.975 / 0.025
U15 99.9995 / 0.0005 99.9975 / 0.0025
U16 99.99995/0.00005 99.99975 / 0.00025
U17 99.999995/0.000005 99.9999 / 0.0001

To avoid problems with In-situ test, always

specify a face scanned filter from the supplier !
Local & Overall Efficiency
H 14 example

@ MPPS Local pen

< 0.025 %
Local pen
< 0.025 %
Local pen
< 0.025 %

Local & Overall

Pen % must pass Overall penetration
< 0.005 % @ MPPS
So, remember the following at this
MPPS for an H14 is ~ 0.2 m dia.
H14 is allowed a local penetration of
0.025 % vs 100% challenge.
GMP in-situ leakage target for an H14 is
0.01% for aerosol having an MMD 0.5
0.7 m.

Now, lets look at aerosols for
In-situ leak testing

BS EN ISO 14644-3
Test Standard
Informative Annex B6 Applies to HEPA & ULPA Filters
Aerosol Photometer Filter Installation Leak Test
For cleanrooms less clean than ISO 5
For filters with MPPS local penetrations > 0.005%
Pneumatic or thermal generation using DOP or
equivalent materials giving an aerosol of MMD
between 0.5 to 0.7 m & SD of 1.7
Upstream Challenge 10 - 100 mg/m3 + sensitivity
comments for conc < 20 mg/m3
Leaks designated as readings > 0.01% (guidance

BS EN ISO 14644-3
Test Standard
Informative Annex B6 Applies to HEPA & ULPA Filters
DPC Filter Installation Leak Test
For cleanrooms cleaner than ISO 5
For filters with MPPS penetrations < 0.005%
DOP or DEHS challenge enhancement if required
to obtain adequate sensitivity.
Isokinetic sampling and defined scanning rate
required for valid results.
Leaks designated as readings > an acceptance
value calculated from the MPPS of the filter.

Different Aerosol Generators Generate
Different Size Distributions
Thermo-Pneumatic Aerosol Generator

Different Aerosol Generators Generate
Different Size Distributions
Laskin Nozzle
Cold Generator

Photometer is a Mass Spectrometer NOT a
Particle Counter
Aerosol Photometer

Filter Test Aerosols MMD Thermal
by mass 0.2
micron. Near to
filter MPPS

So, now remember the following:

It is quite possible for our test aerosol to

be near to MPPS.
In this situation a good H14 may
apparently fail the 0.01 % leak test
when a Thermo-pneumatic aerosol and
photometer is used.

The special issues of high
temperature filters

High Temperature Filters
Ovens and De-pyrogenisation Tunnels have
some special problems:-
Temperature 250-300 degC.
Thermal expansion & contraction transient particle
shedding .
Oil test aerosols can cause carbon deposits to be left on
Cannot aerosol test hot. Aerosol Leak Test cold,
particle count check when hot.
When conditioned, filters at best are H 13 Local
Penetration allowed is 0.25%, a long way from 0.01%.

How to resolve the problems!

Resolving the problems

Risk-based GMP is all about Science vs

Compliance. Have faith in your science!
Agree a leak test acceptance for an H14 of
0.03%, or 0.01% if a x2 filter is specified.
Process High Temp HEPAs
Agree cold leak test acceptance for an H13, say
0.20%, or 0.1% if a x2 filter is specified.
Recognise the limitations on leak testing these
filters. Hot particle count classification may be
more important & relevant.

EN 1822-1 Filter x2 vs x5 Option

Overall Effic/Pen Local Effic/Pen

Local efficiency = 5x 0verall
H13 99.95 / 0.05 99.75 / 0.25 %
H14 99.995 / 0.005 99.975 / 0.025
Local efficiency = 2x 0verall
H13 99.95 / 0.05 99.75 / 0.10 %
H14 99.995 / 0.005 99.975 / 0.01

In-Situ Testing -Summary
Select test method, aerosol & generator.
Determine the acceptance criteria and justify.
Agree repair/replacement criteria.
Determine challenge up-stream.
Scan test final filter face for leaks
Determine acceptance or rejection.

Be aware of the Filter Standards
Specify filters correctly
Install carefully
Test In-situ, define appropriate
acceptance criteria
Plan re-testing, rationalise frequency
based on track record of the application
and process criticality.
Have faith in risk-based.
Keep records

This presentation has been prepared
and delivered by:-
Gordon J Farquharson
Bovis Lend Lease Technology
Consultants and Engineers
Tanshire House
Shackleford Road
Surrey, GU8 6LB
tel +44 1252 703663
fax +44 1252 703968