Select the right air filtration solution from scalable formats for applications including stainless steel, high-temperature, highly oxidizing and single-use operations.
Efficient and reliable membrane air, gas and vent filtration is fundamental at all stages of biopharmaceutical production to protect the critical quality attributes of drug products and, ultimately, patient safety. Sterilizing-grade air filters protect biopharmaceutical products from contamination by microorganisms or particles during processes such as gas venting from tanks or bioreactors, compressed gas filtration, and high-temperature or highly oxidizing situations. Non-sterilizing filters reduce bioburden for non-critical applications.
Pall has leveraged its filtration expertise to build an air filtration product portfolio that meets the stringent quality requirements of all biopharmaceutical applications. High-quality hydrophobic membranes in a broad range of scalable formats address air filtration needs from trial to cGMP environments. Pall’s air filtration solutions include a range of filter cartridges and filter capsules to cover the requirements of both stainless-steel and single-use processes.
When selecting the right air filtration solution, it is critical to consider not only filter type and size but also process operating conditions such as sterilization methods, temperature, regulatory requirements, and integrity testing requirements.
Air and gas-sterilizing filtration for stainless steel systems
Many applications in critical biotech operations require the highest level of sterility assurance. Sterilizing-grade air filters can be used to filter inert compressed gases and provide vent filtration for holding tanks and bioreactors. The nature of many biopharmaceuticals mean that terminal heat sterilization is not possible; ensuring sterility during final formulation and filling steps through filtration is the last line of defense for product safety. Although sterilizing-grade air filters are designed for use in gaseous fluids, they are validated under “worst-case” conditions by a liquid bacterial challenge test with Brevundimonas diminuta, at a level of 107 organisms/cm2 of filter area.
Emflon® PFR PTFE sterilizing-grade membrane filter cartridges and capsules have been specifically developed as air filters with high strength and long life for nitrogen blanketing or compressed gas applications for stainless steel bioreactors, and filling operations where temperatures are under 60 °C. The hydrophobic and chemically inert filter membranes meet the FDA requirements for microbial removal to qualify as a sterilizing grade filter. The membrane offers a removal rating of 0.2 µm in liquids and 0.003 µm in dry gases.
Sterilizing air filtration in single-use systems
The trend towards single-use systems has a significant impact on air filter selection. Unlike multi-use stainless steel systems which can be steamed in place, single-use bioreactors, biocontainers, and filling operations require filters that are gamma irradiation stable. Users requiring this form of filter sterilization should choose filters that are compatible and validated for gamma sterilization up to 50 kGy.
Emflon® II PVDF sterilizing-grade membrane air filter cartridges and capsules have a high capacity for particulates and are validated for gamma irradiation for use in single-use systems. Emflon II filter capsules can be supplied either pre-sterilized by gamma irradiation or non-sterilized for sterilization by gamma irradiation/autoclave by the end user.
High-temperature, ozonated-water venting and oxygen-enriched applications
Sterilizing-grade filtration in high-temperature, ozonated-water venting, or oxygen-enriched air applications requires a specialized cartridge.
Vent filters on WFI tanks: Vent filters must be fitted to Water For Injection (WFI) storage tanks to provide a sterile barrier and free passage of air in and out of the headspace of the tank. WFI is usually kept at a minimum temperature of 80 °C to prevent microbial growth. The elevated temperature creates an oxidizing environment around the filter.
Ozonated water tanks: When ozone is dissolved in water, it creates a potent and very fast-acting antimicrobial agent that can be used in the production of WFI and Purified Water. As ozone is sparingly soluble in water, it will off-gas and accumulate in the tank headspace and in the air vent filter. Ozone and its breakdown product oxygen are powerful oxidizing agents. The filters should therefore have good resistance to oxidation and be validated for exposure to ozone at concentrations in water typically up to 100 ppb at 40 °C.
Oxygen-enriched air and pure oxygen in cell culture applications: To improve productivity in mammalian and microbial cell culture applications, high-strength broths with higher biomass are being used to achieve improved product yields. These conditions will generate a strong oxygen demand which may not be achievable by simply increasing aeration rates but can be managed by using oxygen-enriched air or pure oxygen. The sterilizing air filters on inlets and outlets to the bioreactor will therefore be exposed to a strong oxidizing environment which could introduce a risk of filter degradation, especially over extended fermentation campaigns. The air filters for these applications should therefore be designed and validated for exposure to oxygen-enriched air and pure oxygen.
Emflon® HTPFR PTFE sterilizing-grade membrane filter cartridges are specially designed for sterile air filtration in highly oxidizing applications such as oxygen enrichment of bioreactors, or process steps with temperatures above 60 °C, such as autoclaves, fermentation inlet air, aseptic packaging/ blow-fill-seal and WFI tank vents. The optimized Emflon HTPFR cartridges have an oxidation-resistant support/drainage, cage and core that has been validated for extended use at elevated temperatures or in highly oxidizing applications.
Non-sterilizing-grade filters can be cost-effectively used for air filtration in non-critical venting and gas applications where high flow rates are required and bioburden reduction is sufficient.
Emflon® PFA membrane gas filter cartridges offer the highest levels of bioburden reduction and high flow rates through optimized membrane combined with a high filter area per 254 mm (10 in.) cartridge.
Protection of sterilizing-grade filters in air and gas applications
A pre-filter may be beneficial in some processes to reduce the change-out frequency of a more specialized membrane air filter, such as a sterilizing-grade filter. Pre-filters can provide cost and operational benefits in circumstances where high levels of contaminants are present in the gas feeds, such as dry powder systems, and where the final filter will be used for extended periods of time.
HDC® II all-polypropylene filter capsules and cartridges incorporate proprietary HDC II tapered pore polypropylene depth media and are available in a range of different formats. HDC II filters are useful for fine particle and prefiltration applications where purity, reliability, and economy are critical.