This article identifies a suitable design for redundant filtration operations using single-use technology and standardised assembly components. The design was finalised with input from a global technical and quality team with consideration given to international regulatory requirements. The article also demonstrates the capability of the assembly to withstand the high pressure that is used for integrity testing and drying. Pre-use integrity testing was performed on both filters. Using hydrophilic/hydrophobic filters on the assembly outlet eliminated flush volume limitations caused by catch bag size. Assembly specifications, such as leachables and extractables, hold up volume and flushing requirements, were established for a single-use assembly.
Meeting regulatory expectationsAs defined in PDA Technical Report 26, redundant filtration is a "type of serial filtration in which a second sterilising-grade filter is used as a backup in the event of an integrity failure of the primary sterilising filter." The pore size of the sterilising-grade filters may be the same or tighter than the primary filter (1). Other regulatory bodies (e.g., FDA, EMA and SFDA) have also issued their own guidelines for sterile filtration. According to the FDA's aseptic processing guidelines published in 2004, it is recommended that redundant filtration should be considered in many cases where liquid is sterilised by filtration (2). The EMA's 2008 GMP guidelines state that because of potential risks of sterilisation by filtration, a second filtration step as close to the filling point as possible is advisable (3).
Designing a redundant filtration system that meets regulations and recommendations is challenging. For stainless steel systems, the EMA recommends that integrity testing should be performed on sterile filters before use. To do this, filters must be fully wetted without breaching the sterility on the downstream side of the assembly. Many conventional stainless steel facilities employ a "catch can" with a sterile vent filter to collect the initial flush liquid from the wetting step. Prior to use, additional time is required to sterilise, maintain and store the catch can. In addition, use of a catch can constrains the total flush volume that can be used if the filters need to be rewetted (e.g., in a repeated filter integrity test).
Disposable or single-use redundant filtration (SURF) assemblies offer a flexible solution for this relatively complex operation (4). These assemblies can be presterilised by the supplier using gamma irradiation and there is no need for cleaning after use because assemblies are self-contained and entirely disposable.