Abstract Virus filtration is a key component of the overall virus clearance strategy in the production of monoclonal antibodies. These virus filtration membranes also provide one of the most selective membrane separations ever demonstrated, with more than 95% recovery of the antibody product in the filtrate with more than 99.99% retention of even small parvovirus, despite the less than 2-fold difference in size between the virus and antibody. However, there is currently no quantitative data on the intrinsic sieving characteristics of commercially available virus filters. Experiments were performed with the Viresolve® Pro and Pegasus™ SV4 virus filters both with and without stirring to control the effects of concentration polarization. The actual sieving coefficient of a highly purified monoclonal antibody was less than 0.05 for both membranes, demonstrating that the high antibody recovery during typical virus filtration processes is a direct result of the high degree of concentration polarization in these systems. The intrinsic selectivity of the virus filter was in good agreement with predictions of available hydrodynamic models accounting for a log-normal pore size distribution. The actual sieving coefficient also decreased with increasing antibody concentration, consistent with available models for proteins with attractive interactions (negative values of the interaction parameter). These results provide important insights into the transport characteristics of virus filters and their effect on the performance of these virus filters in bioprocessing.

中文翻译：

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病毒过滤膜对抗体的保留：极化和筛分效应

摘要 病毒过滤是单克隆抗体生产中整体病毒清除策略的关键组成部分。这些病毒过滤膜还提供有史以来最具选择性的膜分离之一，尽管大小差异不到 2 倍，但滤液中抗体产物的回收率超过 95%，即使是小细小病毒的保留率也超过 99.99%在病毒和抗体之间。然而，目前还没有关于市售病毒过滤器固有筛分特性的定量数据。使用 Viresolve® Pro 和 Pegasus™ SV4 病毒过滤器在搅拌和不搅拌下进行实验，以控制浓差极化的影响。对于两种膜，高度纯化的单克隆抗体的实际筛分系数均小于 0.05，证明典型病毒过滤过程中的高抗体回收率是这些系统中高度浓度极化的直接结果。病毒过滤器的固有选择性与考虑对数正态孔径分布的可用流体动力学模型的预测非常一致。实际筛分系数也随着抗体浓度的增加而降低，这与具有吸引力相互作用（相互作用参数的负值）的蛋白质的可用模型一致。这些结果为病毒过滤器的传输特性及其对这些病毒过滤器在生物加工中的性能的影响提供了重要的见解。