- BioPharm International
Jun 1, 2006
By: Reinhard Baumfalk, Jerry Finazzo
BioPharm International
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The four integrity test steps are implemented upstream and downstream of the
filtration unit in order to be able to detect any possible changes in filter element
properties and thereby supply positive results to confirm the success of the filtration
step. The diffusion test and the bubble point test are established, non-destructive test
methods. To determine validity, compare the test results to the filter manufacturer's
tolerance data. The bases of the tolerance data are validation processes conducted by
the manufacturer. These are used to determine tolerances by correlating absolute,
destructive test methods (bacteria challenge test) with filter integrity tests. Both test
methods rely on a procedure of wetting the filter membrane with a pre-defined
medium (typically ultrapure water, but also customer-specific liquids).4
To start the automatic filter test, the filtration housing is disconnected from the actual
process, or the filter is installed in a separate test housing. In this procedure, the filter
element is pressurized at a specific value on the upstream (non-sterile) side. At this
test pressure, the diffusion through the filter membrane is determined for values
starting at 0.1 mL/min. By contrast, when the bubble point test is carried out, the
applied test pressure is raised successively and the diffusion measured in parallel is
monitored to determine any disproportionate increase. This increase in diffusion is
caused by the wetting medium being pressed out of the pores of the filter membrane,
which initially occurs in the largest pores, thereby providing information about the
upper limit of the pore size distribution. Typical bubble point values for microfilters
range between 3,000 mbar and 4,000 mbar and, in ultrafiltration, can go up as high as
8,000 mbar. These methods also allow reliable detection of cracks or blockage.
Air filtration also needs a filter integrity test method to guarantee the sterility of
critical parameters. Applications for these filter elements include pharmaceutical and
biotechnological production systems. Unlike liquid filtration, air filtration elements
are based on hydrophobic membranes, which prohibit the test methods previously
mentioned (membrane wetting with ultrapure water).
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White Papers and Air filtration also needs a filter integrity test method to guarantee the sterility of critical
Vendor Notes parameters.
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White Papers and Air filtration also needs a filter integrity test method to guarantee the sterility of critical
Vendor Notes parameters.
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Marketplace/ class 2 or 3).8 Since integrity testers are not only used in a well-defined laboratory
Technology environment, but also installed in a rough production process, the integrity tester
Showcase Guidelines manufacturer has taken these conditions into consideration. Hardware components should
Marketing Services be made of appropriate materials (stainless steels are favored) and have the needed
Lists process reliability. Software has to cover the normal operating conditions, and also be able
Reprints to detect critical changes of process parameters such as temperature or supply media
Subscriptions (pressurized air). Often, these requirements are met by an automated functionality test or
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separate software control loops within the test procedure.
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Talk to BioPharm To meet the needs of process integration, most of the available integrity testers have
Contact Marketing interfaces in order to use additional external hardware. External valves mounted on the
Services filter housing can be handled directly, or controlled by sending commands via a PLC
Contact Editorial interface. External sensors can be connected in order to perform the measurement directly
at the filter housing, because long tubing lengths could interfere with the accuracy of the
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measurement.
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Because the WIT and WFT test use WFI as penetration media for the
filter membranes, additional dedicated equipment has been
developed by most of the integrity test manufacturers. A trolley
equipped with a stainless steel vessel stores the needed water
volume under sterile conditions. A PLC allows automated CIP or even
SIP procedures for the vessel, with valves permanently connected.
Filter Integrity
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Reinhard Baumfalk
PhD
About Reinhard Baumfalk
email: reinhard.baumfalk@sartorius.com
See more articles by Reinhard Baumfalk
Jerry Finazzo
Product Manager
About Jerry Finazzo
email: jerry.finazzo@sartorius.com
See more articles by Jerry Finazzo
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Marketplace/ or time based) and manually. It is important that the data be transferred in a timely fashion
Technology to a designated computer where the data can be properly archived and backed up. While
Showcase Guidelines integrity testers may have the memory to store large amounts of data, they are not
Marketing Services intended as the sole data storage location for integrity test data (transient data).
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Subscribe or Update described as the "stand alone" setup is based on the capability of the state-of-the-art
Your Subscription devices to process and store data. The device is only connected from time to time to the
Talk to BioPharm process network containing the archive servers or MES systems. This device needs to
Contact Marketing have the capability to store data (integrity test parameters as well as test results) since
Services GMP-relevant data are being stored. An audit trail, or user access management, is
Contact Editorial required since all 21CFR Part 11 requirements have to be met in the device.
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Board In the second setup, the devices are permanently connected to the process network. Due
to this permanent connection, in most cases all relevant GMP data are not stored on the
device, but directly received from or sent to the MES or PLC system ("unique source
principle"). The supervising network can handle the start of integrity tests and running the
complete test procedure. Since GMP data are not stored on the integrity test device, it is
only a part of a 21 CFR Part 11 system.
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Reinhard Baumfalk
PhD
About Reinhard Baumfalk
email: reinhard.baumfalk@sartorius.com
See more articles by Reinhard Baumfalk
Jerry Finazzo
Product Manager
About Jerry Finazzo
email: jerry.finazzo@sartorius.com
See more articles by Jerry Finazzo
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Marketplace/
Installation qualification. A qualification generally starts with the IQ. The purpose of the
Technology
Showcase Guidelines IQ is to provide documented verification that the integrity tester complies with approved
design intentions and the manufacturer's recommendations or requirements. Verification
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that the proper documentation has been supplied with the unit, a physical inspection of the
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equipment, and a facility requirements check are common items included in the IQ.
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Your Subscription Operational qualification. The purpose of an OQ is to provide documented verification
that the equipment performs as intended. There are many items verified during an OQ,
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with some of the more difficult tests confirming that the actual integrity test result is within
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specification. Typically, for bubble point, diffusion (forward flow), and water intrusion, the
integrity test result will be compared with a measured reference. For example, when
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testing for diffusion, it is common for the integrity result to be verified using a mass-flow
Contact Circulation meter. IQ and OQ can be performed by the manufacturer of the integrity tester, or by the
Editorial Advisory end user. Similarly, the IQ and OQ protocols will typically originate from the manufacturer,
Board with the end user using them as is, or modifying them to their validation standards.
Performance qualification. The last part of a validation is the PQ. The purpose of a PQ is
to provide documented verification that the equipment can perform effectively and
reproducibly based on approved standard operating procedures (SOPs). Typically, actual
process filters in the production environment are used during this testing. The end user's
SOPs, as well as personnel, are used to perform the PQ. The integrity tester manufacturer
may be consulted during the PQ, but typically will not perform the protocols.
CONCLUSION
Quick Recap
Pages | 1 | 2 | 3 | 4 | 5
Reinhard Baumfalk
PhD
About Reinhard Baumfalk
email: reinhard.baumfalk@sartorius.com
See more articles by Reinhard Baumfalk
Jerry Finazzo
Product Manager
About Jerry Finazzo
email: jerry.finazzo@sartorius.com
See more articles by Jerry Finazzo
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© 2007 Advanstar Communications, Inc.. All rights reserved.
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