Gas Filtration Sterile Micro Filtration For Bio Reactors F & S Vol 43, #4, May 06
Gas Filtration Sterile Micro Filtration For Bio Reactors F & S Vol 43, #4, May 06
Gas Filtration Sterile Micro Filtration For Bio Reactors F & S Vol 43, #4, May 06
Feature
Gas filtration:
Pharmaceuticals, biotechnology, and healthcare are high growth segments for the filter market due to the broad growth of aseptic and sterile processing. The present cartridge filter market is about US$2 billion per year with a projected growth rate of 9 percent. This article is focused on the sterile filtration of gases used for the fermentation process and fermenter/tank vent applications.
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Brand Name Microfluor II Emflon Durapore Aervent Aerex Sartofluor GA High Flow Tetpor H.T.
MOC Hydrophobic PTFE Double-layer hydrophobic PTFE Hydrophobic PVDF Hydrophobic PTFE Hydrophobic PTFE Hydrophobic PTFE Expanded PTFE
conditions. This is particularly true of vent filter sizing and the manufacturer will require further information about the tank to be vented, to determine the proper sizing for this application.
Filter housings
The size of the filter housing is determined by the nearest selection of size and number of filter cartridges required to meet gas filtration requirements. The selection of the filter housing type is restricted to the inline style or the T style which are given the position of the inlet and outlet connections in relation to the filter cartridge. The T style housing is the most common choice for two reasons it is easier to install; and to configure with a cleaning cap and spray ball for cleaning in place. If you are steaming in place, or your operating pressure is above 15 psig, the filter housing should be purchased as a registered pressure vessel built to ASME Section VIII Division 1 code.
condensing steam. During normal processing conditions the vent filter allows the tank to breathe sterile air, but precautions need to be taken to ensure that during the process steps the filter does not become wetted or blocked by powders (process materials) from process additions to the tank.
liquid challenge test with Brevundimonas diminuta ATCC 19146. This evaluation is done based on the complete removal of greater than 107 colony forming units (cfu) per cm2 of effective filtration area. Filter manufacturers will normally perform an aerosol challenge test demonstrating 100% Brevundimonas diminuta removal, as well as a viral and bacteriophage aerosol challenge test. Note that there is no standardised test procedure for these aerosol challenges. Filter manufacturers will also perform a sodium chloride aerosol test using a condensation nuclei counter (CNC) to determine the particulate removal rating in gas.
Filter sizing
The gas inlet and vent filters are sized to meet the highest flow conditions at the worst case process conditions to be effective throughout the operation of the process. The sizing should take into account the following conditions, to determine the highest flow and worst case process operating conditions before sizing the filter: Forward or reverse flow conditions Normal operating maximum flow and pressure conditions; Maximum flow and pressure conditions during SIP; Maximum and dirty clean pressure drops. The sizing of the filter is best left to the filter manufacturer who will determine the best filter selection based on all of the above operating
Features of the ideal air filter Ability to retain organisms through the full range of usage; High-flow rates at low pressure drop; Ease of installation; Ability to in situ integrity test; Can withstand multiple steaming cycles; Compatible MOC (Material Of Construction); Low extractable levels; Regulatory compliant and Validatable.
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Feature
exposed to a set pressure upstream of the membrane. The pressure upstream of the filter is monitored to determine the flow rate (based on a know-volume upstream of the filter). The diffusional gas flow rate across the wetted membrane is directly related to the pore size distribution in the membrane. Note that in both Bubble Point and Pressure Decay/Hold tests, thorough flushing of the filter with the alcohol/water mixture is essential to prevent false IT failures.
based on the bacterial liquid challenge test (see hydrophobic filter removal ratings).
Bubble point
In this method, a filter is wetted out using an alcohol/water mixture (used because the filter membrane is hydrophobic). The filter is exposed to increasing air pressure on the upstream side of the membrane, until the pores in the filter
membrane begin to vent, causing a distinct change in the gas flow through the filter. The pressure at which this change occurs is know as the bubble point and is related to the pore size distribution in the membrane.
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condensate load, provide ports for temperature monitoring points and, install sections to hold and recover spore strips for sterilisation studies. It is critical to review how you are going to perform a post SIP IT test without breaking sterility. This is most usually achieved by IT of the filter, once the main vessel has been sterilised and can be used as a sterile reservoir for the filter during IT.
the filter works, and is suitable for their application. The manufacturer is responsible for providing information in support of the end users requirements for details on the filters performance; materials of construction, integrity data correlations to microbial retention; data on the filters range of application; and the validation of the integrity testing of the integrity tester. The filter manufacturers produce validation guides that will include the test methods, test data and support data that you will use to support your validation. As part of your validation effort, the key points that need to be addressed are: Validation of the bacterial retentive properties of the filter on the actual product; Proving that the filter remains integral at the end of the filtration run; Validating the integrity tester used for integrity testing of the filter;
Proving that the filter does not release harmful extractables into the product; Prove that the filter does not adsorb or absorb components of the product formulation.
Summary
Membrane cartridge filters are a very costeffective way to produce sterile gas streams for bioreactors and sterile process tanks. They can be effective when applied correctly, taking into account the application and its process conditions. Finally the filter xmust be validated and this process involves the physical, chemical and biological testing of the filter under extreme process conditions to provide assurance that the filters (when correctly used and integrity tested) will provide a consistently sterile gas stream.
Authors: Jignesh Padia [www.qsvbiologics.com] Process development associate Paul Huntington [Cheme Engineering Inc]
Validation
The user and the filter manufacturer share the responsibility for the validation of the filter application. The user is responsible for final validation testing to ensure that