ASTM E3042-16
用Triton X-100处理灭活啮齿动物逆转录病毒的工艺步骤的标准实施规程

Standard Practice for Process Step to Inactivate Rodent Retrovirus with Triton X-100 Treatment

被代替

标准号

ASTM E3042-16

发布

2016年

发布单位

美国材料与试验协会

替代标准

ASTM E3042-16(2024)

当前最新

ASTM E3042-16(2024)

 

 

适用范围

3.1 Rodent-derived cell lines are widely used in the production of biopharmaceutical drugs such as mAbs and Fc fusion proteins. These cell lines have been shown to contain genes encoding endogenous retroviral-like particles or endogenous retrovirus. Despite the lack of evidence for an association between such rodent retroviruses and disease in humans, the potential contamination of human therapeutics raises safety concerns for biopharmaceutical drugs. Additionally, adventitious agents such as viruses can be introduced into a biopharmaceutical drug substance manufacturing process from other sources, and potential safety issues can be attributed to these potential unknowns. For these reasons, effective viral clearance is an essential aspect of an integrated approach combining safety testing and process characterization which ensures virus safety for biopharmaceutical drug products made using rodent cell lines.

3.2 Solvent/detergent inactivation has been widely used for decades to inactivate enveloped viruses in blood plasma derived biopharmaceutical therapies (1-3).3 Solvent/detergent systems using the detergents Triton X-100 or Polysorbate 80 along with the organic solvent tri(n-butyl)phosphate (TNBP) have been used to inactivate enveloped viruses by disrupting the viral envelope thereby reducing the ability of the enveloped virus to attach to and then infect the host cell (4 and 5).

3.3 Most manufacturers of mAbs, recombinant proteins, and Fc fusion proteins have focused on viral inactivation methods using the detergent Triton X-100 or Polysorbate 80 in the absence of TNBP (6), which can interfere with subsequent bioprocessing steps. The ability of the detergents alone to inactivate retroviruses has been demonstrated in monoclonal antibodies produced in rodent-derived cell lines (6-9). At a 2011 workshop devoted to viral clearance steps used in bioprocessing (7), investigators from one firm showed incubation with 0.2 % Triton X-100 for 60 min of hold time at ambient temperature inactivated >5 log₁₀ of X-MuLV across four separate mAbs in cell culture matrices.

3.3.1 At the same 2011 workshop (7), investigators from a second firm confirmed that levels of protein concentration and lipid concentration had no observable effect on MuLV virus inactivation at levels of 0.3 % Triton X-100. Additionally, eight different monoclonal antibody Host Cell Culture Fluids (HCCF), were treated with 0.3 % Triton X-100 for a 60 minute hold time at 20°C. Effective inactivation, ≥4 log₁₀ of inactivation ......

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