USD 2121

A
p
p
l
i
c
a
t
i
o
n

N
o
t
e
I n tro d u c tio n
Water systems for the production, storage
and distribution of purified water or WFI are
critical points in pharmaceutical production
plants. O ne focus of the regulatory authorities
is the installed vent filter on water
holding tanks.
C o n te n ts
This application note provides our technical
recommendations to meet current regulatory
requirements and to ensure:
Sterile protection of the tank
with E m flo n CPFR or PFR vent filters
Built-in drainage
with A d va n ta AVL filter housings
Prevention of condensate
with A d va n ta Trace Heater
Reliable water intrusion testing
with P a lltro n ic A q u a WI T integrity
test instruments
R e g u la to ry
The combination of A d va n ta housings and
the A d va n ta trace heater avoids condensate
blinding of high flow E m flo n CPFR or PFR
sterile filters and is easy to operate. The
P a lltro n ic A q u a WI T filter integrity test system
automatically performs water intrusion tests
on tank vent filters to assure that these
critical filters still have sterilizing capability
during long term operation or after steam
sterilization.
A summary of the most important features
and benefits of P a lltro n ic A q u a WI T tested
E m flo n CPFR and PFR air sterilizing filters in
A d va n ta housings is shown in the diagrams
and tables on the following pages.
Ve n t F iltra tio n o n
Wa te r fo r in je c tio n WF I ) Ta n k s
Meeting vent filter requirements with Emflon

PFR & Emflon CPFR

vent filters, Advanta
TM
AVL filter housings, Advanta Trace Heater,
Palltronic

AquaWIT
TM
& Palltronic Flowstar
TM
integrity test instruments
In the FDA " Guide to Inspections of
High Purity Water Systems" (1993),
which is fully accessible under:
http://www.fda.gov/ora/inspect_ref/igs
/high.html, regular filter testing and
prevention of condensate formation
are expected for vent filters on water
holding tanks:
"VII. HOLDING TANK
In hot systems, temperature is usually
maintained by applying heat to a
jacketed holding tank or by placing a
heat exchanger in the line prior to an
insulated holding tank. The one
component of the holding tank that
generates the most discussion is the
vent filter. It is expected that there be
some program for integrity testing this
filter to assure that it is intact. Typically,
filters are now jacketed to prevent
condensate or water from blocking
the hydrophobic vent filter. If this
occurs (the vent filter becomes
blocked), possibly either the filter will
rupture or the tank will collapse.
There are methods for integrity testing
of vent filters in place. It is expected,
therefore, that the vent filter be located
in a position on the holding tank where
it is readily accessible..."
In a similar manner, the European GM P
Guide asks for regular testing of vent
filters used in applications such as
vents on water tanks.
Additionally, the ASM E Bioprocessing
equipment guide (ASM E BPE 1997)
defines how equipment must
be designed and installed to be
classed as hygienic. Chapter SD-4.4.
requires that "the filter housing shall be
designed to allow for complete venting
and draining. Vent-type in-line filter
housings should be installed in the
vertical with the condensate/drain port
directed downward." Furthermore,
"Vent filters for hot process services
should be heat traced or steam
jacketed to prevent bacterial contami-
nation (i.e. to maintain hygienic
conditions) via backgrowth through
wetted filter media".
This application note provides our
technical recommendations to meet
current regulatory requirements and to
ensure:
Sterile protection of the tank
with E m flo n CPFR or PFR vent filters
Built-in drainage
with A d va n ta AVL filter housings
Prevention of condensate
with A d va n ta Trace Heater
Reliable water intrusion testing
with P a lltro n ic A q u a WI T integrity
test instruments
R e g u la to ry G u id e lin e s
Ve n t filtra tio n o n wa te r fo r in je c tio n WF I ) ta n k s
Compressed air
Steam
WFI tank
F ig u re 1 : S yste m A
Ve n t filte r in sta lla tio n fo r h o t WF I ta n k s. A sin g le in sta lla tio n with o u t c o n tin u o u s
u se o f th e WF I ta n k d u rin g Wa te r I n tru sio n Te stin g WI T ) o f th e ve n t filte rs.
V6
To atmosphere
V3
F ig u re 2 : S yste m B
Ve n t filte r in sta lla tio n fo r h o t WF I ta n k s. A d o u b le in sta lla tio n is re c o m m e n d e d to a llo w
c o n tin u o u s u se o f th e WF I ta n k a n d Wa te r I n tru sio n Te stin g WI T ) o f th e ve n t filte rs.
P a lltro n ic A q u a WI T
in stru m e n t fo r fu lly
a u to m a tic wa te r
in tru sio n filte r
in te g rity te stin g
Compressed air Compressed air
A d va n ta AVL h o u sin g s
with E m flo n
P F R /C P F R
ve n t filte r a n d
A d va n ta Tra c e H e a te r
WFI tank
Steam Steam
Pressure gauges
for monitoring of :-
downstream
pressure
during WIT
differential pressure
during steaming
V6
V4a
V5a V5b
V9b
V3a
V3b
V2b V1b
V7b
V1b V2a V9a
V7a
V8a V8b
To atmosphere To atmosphere
V9 V2 V1
V7
V8
Pressure gauges
for monitoring of :-
downstream
pressure
during WIT
differential pressure
during steaming
A d va n ta AVL h o u sin g
with E m flo n
P F R /C P F R
ve n t filte r a n d
A d va n ta Tra c e H e a te r
P a lltro n ic A q u a WI T
in stru m e n t fo r fu lly
a u to m a tic wa te r in tru sio n
filte r in te g rity te stin g
V4b
Drain and
condensate trap
Drain and
condensate trap
V4
E m flo n C P F R o r P F R
vent filters for sterility assurance under
moist and high temperature conditions
A d va n ta Tra c e H e a te r
for the prevention of condensate
in operational filter housing
A d va n ta AVL H o u sin g
for built-in drainage of water and easy
WIT testing
A dual system will operate with both or
either of the vent filters in operation
and allows continuous operation of the
WFI tank. A single system has only one
vent filter in operation and therefore
doesn' t allow continuous operation of
the WFI tank during steam sterilization
and testing. An example of how a
system might be operated is detailed
below:
1 . S te a m ste riliza tio n o f filte r
a sse m b lie s
This procedure is the same for
system A or B either of which can
be steamed whilst the other is in
operation. For a single system the
procedure described below can be
used with slight modifications (no
V5). System B only is described.
Normal operation (see below) with
P a lltro n ic A q u a WI T instrument
disconnected from V3B and V9B.
V6, V5A, V5B, V1A and V1B O PEN.
Heat tracing on filter system to be
steamed switched O FF (cool-down
may take several hours).
CLO SE V5B and V1B.
O PEN V8B and V2B until steam
emits, O PEN V3B and V4B.
Partially CLO SE V4B, V3B and V2B.
Leave System to steam for required
period.
O n completion of steaming:
CLO SE V4B, V3B, V2B, V8B and
O PEN V7B with a pressure of
>200mbar (2.9psi) over steam
pressure.
To purge steam out of system
O PEN V2B, V3B and V4B.
System can then be left to dry and
cool down by CLO SING V2B, V3B
and V4B.
O n completion of cooling/drying:
Remove Air : CLO SE V7B, O PEN
V2B and V3B. CLO SE V3B and V2B.
2 . Wa te r I n tru sio n Te st WI T )
Heat tracing on filter system
switched O FF (cool-down may take
several hours).
This procedure is a general one
allowing use of the A q u a WI T test
device. At this point ALL valves on
System B are closed.
Connect A q u a WI T device to V9B
and V3B. O pen V9B and V3B
Conduct test.
Filling and automatic testing is by
V9B and V3B.
O n completion of test:
Drain and dry system (via V9B and
V3B). CLO SE V3B and V9B.
If system required for use switch
heat tracing O N and O PEN V1B
and V5B.
3 . S yste m A a n d B in o p e ra tio n .
V6, V5A, V5B, V1A and V1B O PEN.
All other valves CLO SED.
Heat Tracing on both housings or
on housing in operation switched
O N at tank temperature plus 5C.
System A or B can be isolated by
closing V5A or V5B respectively.
For full details of system operation
contact your local Pall office.
S h o rt D e sc rip tio n o f S yste m O p e ra tio n
A
p
p
l
i
c
a
t
i
o
n

N
o
t
e
F e a tu re s a n d B e n e fits
Features of Emflon CPFR/PFR vent filters Benefits of Emflon CPFR/PFR vent filters
Validated with Brevundimonas diminuta Removal of microorganisms in condensate
in liquids or under moist conditions
Validated with Brevundimonas diminuta, Removal of microorganisms, spores and
Bacillus subtilis spores and phages in aerosol viruses during intended air filtration or vent use
30-days long term aerosol challenge validation Removal of bacteria under long term conditions,
optimized steam sterilization intervals
Validated for steam sterilization at 125C and High pressure and temperature stability during
1 bar (14.5psi) dp in forward direction and at steam sterilization for economic long term use
0.5 bar (7.3psi) dp in reverse direction. 165 hours
steam life at 142C (1 hour cycles)
E m flo n PFR suitable for typically 6 months usage Resistance of filter media and other filter
at 80C or 3 months at 90C. E m flo n CPFR components under high temperature
suitable for typically 12 months usage at 90C conditions in air
Designed to be testable by WIT Reliable filter integrity test, correlated with
(Water Intrusion Test) bacteria removal in liquid
Features of Advanta AVL housings Benefits of Advanta AVL housings
Large 1 1/2" bottom inlet Condensate generated between tank and filter
housing can easily drain back to tank housing can easily drain back to tank
New sanitary valves with non-rotating outlet Improved handling
Vent and drain connection on non - (un)sterile side In-line water intrusion test without risk of microbial
contamination of sterile side
Vent and drain connection with 'Stubli' Easy connection to P a lltro n ic A q u a WI T test
quick coupling devices, therefore easy, fast and safe performance
of a water intrusion test with hydraulic bridge
Features of Advanta electrical trace heater Benefits of Advanta electrical trace heater
Convenient design for A d va n ta housings due to In contrast to steam jackets, no investment
preformed pull over sleeve and silicone insulation cost for valves, pressure regulators or piping
Easy handling and changeout of filter elements as
no steam supply pipes need to be dismantled
Temperature operating range between room Avoids condensate formation on hydrophobic
temperature and 140C with a resolution vent filters. High level of operational safety, as
of 0.1C and a cut-out temperature of temperatures can be controlled exactly
150
O
C5C, controlled by a PT100 sensor
Separate control unit with available cable Position of control unit independent of installation
extensions between control unit and location allows flexible operation and integration
jacket heater into central control facilities
Integrated silicone insulation limit surface Reduced energy consumption
temperatures to typically < 70C
Features of Palltronic AquaWIT integrity test Benefits of Palltronic AquaWIT integrity test
instrument instrument
Fully validated direct flow measurement with Accurate and reliable intrusion testing even under
hydraulic bridge under conditions where the environmental
temperature outside of the filter housing was 20
O
C
higher than water temperature inside the housing.
Validation work has also shown that accurate
measurements can be performed using filter
installations at a distance of at least 10m (32ft)
and a height of 6m (19ft) or more
Supporting Literature is available as follows:
Pall Product
E m flo n CPFR vent filters
E m flo n PFR vent filters
A d va n ta AVL Housings
A d va n ta Trace Heater
P a lltro n ic A q u a WI T integrity test instrument
References:
1. Steam Sterilization of Pall Filter Assemblies
2. The Pall water intrusion test for integrity testing sterile gas filters
3. Czermak and Catapano: Automated integrity testing of hydrophobic filters based on water
intrusion measurements: comparative analysis of a refilling continuous-flow and a pressure
decay batch device.
4. Jaenchen et al: Studies on the theoretical basis of the water intrusion test (WIT)
P le a se c o n ta c t yo u r P a ll sa le s o ffic e fo r fu rth e r d e ta ils o r visit o u r we b site a t www. p a ll. c o m
Copyright 2001, Pall Europe Ltd. ,Pall, Advanta, AqwaWIT, Emflon, Flowstar and Palltronic
are trademarks of Pall Corporation.
Filtration, Separation, Solution is a service mark of Pall Corporation.
indicates a Pall trademark registered in the USA.
Stubli is a trademark of Stubli.
PELEH/01-D.SH/CS/10.2001
2200 Northern Boulevard
East Hills, New York 11548-1289
+1 800.717.7255 toll free
+1 516.484.5400 phone
+1 516.625.3610 fax
pharmafilter@pall.com e-mail
Europa House, Havant Street
Portsmouth PO1 3PD, United Kingdom
+44 (0)23 9230 3303 phone
+44 (0)23 9230 2506 fax
UltrafineUK@pall.com e-mail
Pall Corporation has offices and plants throughout the world in locations including:
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Hong Kong,
India, Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands,
New Zealand, Norway, Poland, Puerto Rico, Russia, Singapore, Spain, South Africa,
Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela.
Distributors are located in all major industrial areas of the world.
Visit us on the web at www.pall.com/biopharmaceutical