ASTM E3259-22 PDF

SIGNIFICANCE AND USE 3.1 Mammalian cell lines are widely used in the production of biological therapeutics, such as monoclonal antibodies and other recombinant proteins. Some of these cell lines, like rodent cell lines, are known to contain genes encoding endogenous retroviral-like particles or produce endogenous retrovirus, but there is no evidence of an association between rodent retrovirus and disease in humans. Adventitious viruses can be introduced into a drug substance manufacturing process from other sources, and contamination of human therapeutics is a safety concern (3). 3.2 Virus filtration, an orthogonal technology in a virus clearance platform to such steps as low pH or surfactant inactivation, has traditionally been accepted as a robust method for virus clearance when well designed. Size exclusion has been shown to be the primary mechanism of virus removal by virus retentive filtration, that is, larger viruses are more easily retained than smaller viruses such as parvoviruses (4, 5). Large virus retention has also been shown to be insensitive to process fluid characteristics such as protein type, protein concentration, pH, and ionic strength (4, 6, 7, 8, 9, 10). In contrast, for small viruses, aspects like flow pausing and/or flux decay can impact clearance (4, 6, 11). 3.3 Large virus retentive filters, or retrovirus filters, are tested for removal of larger enveloped viruses like retrovirus or MuLV (80 nm to 100 nm) and have undetectable levels of the large bacteriophage PR772 (64 nm to 82 nm) (1). Small virus retentive filters, or parvovirus filters, are designed to remove parvovirus, like MMV (18 nm to 26 nm) (1). Since size exclusion has been demonstrated as the mechanism of virus retention, retroviruses, which are three to four times larger than parvoviruses, should be large enough to be completely retained, with undetectable levels of retrovirus in the filtrate, by all small virus retentive filters designed to remove parvovirus. 3.4 Numerous published studies... SCOPE 1.1 This practice assures 6.0 log10 removal of retrovirus (for example, MuLV). 1.2 This practice is applicable to monoclonal antibody (mAb), immunoglobulin G (IgG) fusion proteins, recombinant proteins, or other proteins produced using mammalian cell lines (for example, Chinese hamster ovary (CHO), murine hybridomas, murine myelomas, or human embryonic kidney (HEK) 293). 1.3 The step is performed on cell-free intermediates. 1.4 The log removal claim for retrovirus by small virus retentive filters can be used in conjunction with other clearance unit operations (for example, low pH inactivation, or inactivation of virus by surfactant) to assure sufficient total process clearance of potential virus contaminants, which would be supportive of early phase (clinical phase 1 or phase 2a trials) regulatory filings. 1.5 Retrovirus removal claim by filtration is limited to small virus retentive filters, as defined in the PDA Technical Report Virus Filtration (1)2 in the context of this standard. 1.6 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 1.7 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.8 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.