title: Integrity testing of Planova™ BioEX virus removal filters used in the manufacture of biological products.
abstract: Confirmation of virus filter integrity is crucial for ensuring the safety of biological products. Two main types of virus filter defects may produce inconsistent and undesirable performance in virus removal: improper pore-size distribution across the membrane; and specific damage, such as tears, broken fibers, or pinholes. Two integrity tests are performed on each individual filter manufactured by Asahi Kasei Medical to ensure the absence of these defects prior to shipment. In this study, we verified that typical usage of Planova™ BioEX filters would not improperly shift the pore-size distribution. Damage occurring during shipment and use (e.g., broken fibers or pinholes) can be detected by end-users with sufficient sensitivity using air-water diffusion based leakage tests. We prepared and tested filters with model pinhole defects of various sizes to develop standard acceptance criteria for the leakage test relative to porcine parvovirus infectivity logarithmic reduction values (LRVs). Our results demonstrate that pinhole defects at or below a certain size for each effective filter surface area have no significant impact on the virus LRV. In conclusion the leakage test is sufficiently sensitive to serve as the sole end-user integrity test for Planova™ BioEX filters, facilitating their use in biopharmaceuticals manufacturing.
authors.affiliation: Bioprocess Technology Development Department, Asahi Kasei Medical MT Corporation, 5-4960 Nakagawara, Nobeoka, Miyazaki 882-0031, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Medical Material Laboratory, Medical Products Development Division, Asahi Kasei Medical Co., Ltd., 5-4960 Nakagawara, Nobeoka, Miyazaki 882-0031, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Komuro
authors.affiliation: Technical Marketing Department, Bioprocess Division, Asahi Kasei Medical Co., Ltd., 1-105 Kanda Jinbocho, Chiyoda-ku, Tokyo 101-8101, Japan. Electronic address: souka.tb@om.asahi-kasei.co.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sohka
authors.affiliation: Technical Marketing Department, Bioprocess Division, Asahi Kasei Medical Co., Ltd., 1-105 Kanda Jinbocho, Chiyoda-ku, Tokyo 101-8101, Japan.
authors.forename: Terry
authors.initials: T
authors.lastname: Sato
mesh_terms: D005374:Filtration / Q000295:instrumentation* / Q000379:methods; D008567:Membranes, Artificial; D014780:Viruses / Q000737:chemistry*
chemical_list: D008567:Membranes, Artificial
keywords: Air/water diffusion-based leakage test; Biologicals; Forward/diffusive flow; Integrity testing; Planova™ BioEX virus filter