Preuse Post-Sterilization Integrity Testing Best Practices

Preuse post-sterilization integrity testing (PUPSIT) is recommended by most regulators for critical sterilizing liquid filters used in aseptic processing. A preuse test before sterilization will confirm that a filter is installed properly and was not damaged during shipment or handling. Performing a preuse test afterward can detect damage from the sterilization cycle itself. That can limit risk, making it current industry practice especially for products marketed in the European Union. But such testing can be difficult without breaching system sterility.

In this article from BioProcess International, a team of authors from Merck describes an approach using a self-venting, all-in-one sterile barrier membrane filter and also provides filtration line design considerations for implementing such barrier filters.


Barrier Filters
Millipak and Millidisk barrier filters are stacked-disc devices that combine hydrophilic and hydrophobic sterilizing-grade Durapore membranes, both on the top and bottom of each disc (Figure 1). Because of that unique combination of different membranes in parallel configuration, the devices can filter condensate, steam, wetting liquid, and gases without compromising the sterility of a steam-sterilized, autoclaved, or gamma-irradiated system.

Barrier filters can be used downstream of sterilizing-grade filters to maintain system sterility. Water can pass through the hydrophilic discs during a flushing sequence; air can pass through the hydrophobic discs during integrity-test and drying sequences. A barrier filter acts as an automatic vent during testing and drying phases. The volume of particle-free water and air that can pass through these filters is unlimited.

Flushing and Testing Critical Product Filters
Although filter rewetting and retesting should remain an optional activity when preparing a product final filter (sterilizing-grade filter) in line, the PDA Technical Report 26 suggests up to three repetitions (3). The number of retests should be considered when sizing for a flush bag. Barrier filters could provide a more versatile solution.

Filters that are not wetted efficiently the first time could give false failed test results. If rewetting volume is limited, end users might discard integral filters that only marginally failed because of improper wetting. Doing so could lead to unnecessary quality investigations as well as downtime associated with setting up a system again before use. Using a barrier filter allows for rewetting and retesting with ease. Unlimited volumes of particle-free water can be filtered through them to wet these filters efficiently. Using a flush bag and/or catch-can instead creates a large footprint and could limit rewetting. Figure 2 summarizes the advantages and disadvantages of each sterile boundary method available.

Barrier filters also allow extractables flushing through a sterile boundary to drain. A barrier filter also can be used as a vent in system cooling after steam-in-place (SIP) sterilization and in filter drying after flushing to minimize product dilution.

Learn more PUPSIT best practices in this article from BioProcess International magazine.

Author: bpimagazine

BioProcess International™ is a monthly, controlled-circulation magazine devoted to the development, scale-up, and manufacture of biotherapeutics and biodiagnostics. Each issue provides the global industrial biotherapeutic community with up-to-date, peer-reviewed information detailing the business, politics, ethics, applications, products, and services required to successfully drive biopharmaceuticals, vaccines, and biodiagnostics through the development and manufacturing process. BioProcess International™ is part of Informa, plc, a leading international provider of specialist information and services for the academic, professional and business communities. Informa offers a world-class portfolio of publications, events and data services for researchers, students, lecturers and professionals in the academic and scientific communities worldwide.

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