Escolar Documentos
Profissional Documentos
Cultura Documentos
M.W.Jornitz
The Water Intrusion Test, based on the use of water as the testing medium, can be integrated to
autoclave processes by using an external pressure sensor. This article discusses the IQ/OQ
instructions and the SOP to conduct the WIT with an external pressure sensor linked with the PLC of
the autoclave, on hydrophobic membrane filters used for the sterile venting of autoclaves.
P0 x t
1
The pressure drop is caused by the intrusion of water into the pores of the PTFE
membrane can be accurately measured by a sensitive pressure sensor fitted on the top part
of the filter housing. The upstream volume (Vm) imposed by the compacting of the cartridge
at 2,5 bar (standard test pressure) depends on the cartridge size, the pipework configuration
on the top part of the housing and the filling conditions of the filter assembly. That means that
a filtration system filled with a reproducible process, will produce a constant air volume. The
upstream volume determination and its reproducibility are the key points of the validation
procedure proposed in this article.
Qualification of an equipment designed for automatic integrity testing
Many autocalves vent filters are positioned such that access for integrity testing is
extremely difficult and manual WIT procedures under these circumstances are not so
practical. This is the main reason why such equipment requires a fully automatic method
which only involves the measurement of the pressure drop during the test. In order to
calculate the maximum pressure drop allowed in a filter system, the airspace volume above
the water must be determined by mean of an integrity test device measuring the upstream
volume, in this case a Sartocheck 3. The qualification of a new plant designed for an
automatic Water Intrusion Test will therefore focus on the following objectives :
where WIT max is the Intrusion rate limit value established in correlation
with the HIMA bacteria challenge test, and Vm the upstream volume in ml ( VM - Vmo.).
2
IQ/OQ instruction and establishment of the validation certificate : The tests required for
the validation of the filter system shown in figure 1 are conducted 3 times on 3 cartridges
from different batches according to the following procedure :
• Determination of Vmo
• Waterfill of the filter housing: open V1, V2, and V3
• Vent the compressed air volume produced during the filling operation : close V1
and V2, open V4
• Connect Sartocheck 3
• Start a WIT program ( printing of the VM, pressure drop and WIT values )
• Calculate Vm = VM - Vmo
• Calculate the maximum allowed pressure decay (equation 2)
• Compare the pressure drop measured by sartochek 3 and the pressure sensor
• Disconnect Sartocheck 3
• Drain the housing : open V2 and V7
• Dry the cartridge : close V2 and V7. Open V3, V5 and V6 during 10 minutes.
Table A shows the results obtained for the test set up illustrated in figure 1. This document is
supplied as a qualification document for the individual filter assembly.
Table A : Determination of the maximum allowable pressure drop. This data is installed in
the software of the machine as the limite value for an integer filter.
3
PLC Vmo sartocheck
air VENT V4
4 bar PI
V3
V6
CHAMBER
V1 V7 V2 V5
pressure
regulator DI
2,5 bar WATER
20 °C
4
WIT on autoclaves inlet filters.
In the case of a standard sterilizer, the WIT has to be performed after the steam
sterilisation of the filter and prior to the autoclaving cycle as described in the following
sequence :
Steam sterilisation of the filter : the filter is steam sterilised during the autoclaving cycle. The filter
housing is designed with a condensate chamber base to allow the upstream condensate to be
collected. The critical sterilisation temperature is controlled on the downstream side of the filter and
the pressure regulation is achieved by the steam supply pressure regulator at 1,5 bar for 121 °C.
Cooling procedure : Before starting the WIT, the filter assembly must be cooled down and dried
which can be done by an air flow through the cartridge or a vacuum pump. The filter is then prepared
to be tested, the upstream side of the housing can be filled with water and the WIT is performed
during 20 minutes.
Water Intrusion Test : During the 10 minutes stabilisation period the head pressure is maintained at
2,5 bar through via a pressure regulator. The pressure decay in the housing is measured by the
pressure sensor and transduced to the process control system. After testing, the water is drained out
and the filter is dried again, if applicable.
5
Steam
PI
V9 V1
Vent
Vm
V7 V4
Cham ber
Pressure W ater
R egulator
2.5 bar
Vacuum
pum p V2
Condensate C ondensate
WIT
PHASE Chamber Sterilisation Drying Draining Drying
cooling vacuum
VALVES evacuation Cycle of the filter break Filling Test of filter of the filter
6
CONCLUSION
It can be concluded that the use of a sensitive external pressure sensor enables fully
automatic in-situ testing of hydrophobic membrane filters. Being installed on top of the
housing, temperature influences are minimized. Furthermore the use of the sensor technique
enables the direct link to the PLC of the specific systems and therefore makes the test fully
automatic. This fact makes the filter test highly accurate and reproducible, additionally it is
practical and easy to perform. Collected experience with different installation verified these
factors. Moreover filter vendors technical services can support equipment manufacturers in
setting up the right filter assembly, in selecting adapted pressure regulators and pressure
sensors required for the reability of the automatic testing and will provide IQ/OQ instructive
guidelines together with qualification documentation. The W.I.T., conducted automatically, in-
situ, after the sterilisation, without putting the integrity of the plant at risk, meets all the
requirements of the biopharmaceutical industry.
References
1. Health Industry Manufacturers Association Document Nr 3, Version 4 (April 1982)
2. T.H. Meltzer et al, « The Hydrophobic Air Filter and the Water Intrusion Test », Pharm. tech. Sept. 94
P.76 - 84.
3. Michael Dosmar et al, « The Water Pressure Integrity Test for Hydrophobic Membrane Filters » J.
Paren. Sci. Tech 46(4), 102-106 (1992).
4. P. Waibel, « Integrity Testing Hydrophobic Membrane Filter Cartridges with the Water Intrusion
Test », Parenteral Drug Association Meeting, Chicago, March 1994.
5. Validation guide of SARTOFLUOR GA.
6. S.R. Parks et al, « A system for testing the effectiveness of microbiological air filters»European J.
Paren. Sci. Vol. 1 N°. 3 1996
.