Virus Retentive Filters

Abstract

Ensuring the absence of detectable viruses in biopharmaceutical products is imperative from both a regulatory and patient safety standpoint. Biopharmaceutical viral safety is the result of multiple orthogonal barriers operating in concert; incorporation of virus clearance methods is an important strategy to achieving product safety. Filtration through virus retentive filters is currently a key unit operation during the production of biopharmaceuticals and plasma‐derived products. Careful process design and appropriate validation are critical for the successful implementation and performance of virus retentive filters. Here we elaborate on both process design and validation information, describe virus filters currently on the market, and discuss the historical experience with virus retentive filters as reported in the scientific literature. Detailed information for filter users can be found in a comprehensive technical report (TR 41) promulgated by the Parenteral Drug Association (PDA) (1).

Mechanistic failure mode investigation and resolution of parvovirus retentive filters

“…Small virus retentive filtration (VRF) is a key unit operation in the comprehensive viral clearance package for biopharmaceutical and plasma‐derived products . VRF is generally considered to be a robust unit operation; small virus retentive filters are expected to provide greater than 4 log 10 clearance of parvovirus‐sized (or larger) virus particles and near complete clearance of larger viruses of concern like retroviruses.…”

Effects of a pressure release on virus retention with the Ultipor DV20 membrane

“…Virus filtration is a well‐established method for minimizing the inherent risk of viral contamination in the production of both therapeutic proteins (Miesegaes et al, ) and potable water (Madaeni et al, ). Commercial virus filters are available with a variety of pore structures, morphologies, and materials of construction (Miesegaes et al, ). Most filters for bioprocessing applications employ multiple layers of membrane to achieve the very high degree of virus retention required by regulatory agencies.…”

Viral clearance for biopharmaceutical downstream processes

“…Design space conditions established with a phage is considered predictive of filter clearance of the corresponding mammalian virus. Note, however, that current regulatory expectations for filter validation studies for submission to regulatory authorities use mammalian viruses [34].…”

“…Studies have to be done to ensure that there is no bleedthrough of parvovirus when virus filters are used [33]. Data for virus retentive filters have been summarized in a publication by Miesegaes et al [34]. Process operating ranges and depressurization have been reported to impact virus bleed through for virus-retentive filters designed to remove parvoviruses [35].…”