Isu Solomon, Chen Shu-Ting, Daneshpour Raheleh, Shirataki Hironobu, Strauss Daniel, Zydney Andrew L, Qian Xianghong, Wickramasinghe Sumith Ranil
Ralph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR 72701, USA.
Scientific Affairs Group, Bioprocess Division, Asahi Kasei Medical, Chiyoda, Tokyo 100-0006, Japan.
Membranes (Basel). 2025 Jan 17;15(1):34. doi: 10.3390/membranes15010034.
Virus filtration is used to ensure the high level of virus clearance required in the manufacture of biopharmaceutical products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal antibody molecules, particularly at high antibody concentrations. While size exclusion chromatography is generally unable to detect these reversible aggregates, dynamic light scattering may be used to determine their presence. Flux decline during virus filtration may be minimized by pretreating the feed using a membrane adsorber in order to disrupt the reversible aggregates that are present. The formation of reversible aggregates is highly dependent on the monoclonal antibody and the feed conditions. For the pH values investigated here, pretreatment of the feed using a hydrophobic interaction membrane adsorber was the most effective in minimizing flux decline during virus filtration. Ion exchange membranes may also be effective if the monoclonal antibody and membrane are oppositely charged. Consequently, the effectiveness of ion exchange membrane adsorbers is much more dependent on solution pH when compared to hydrophobic interaction membrane adsorbers. Size based prefiltration was found to be ineffective at disrupting these reversible aggregates. These results can help guide the development of more effective virus filtration processes for monoclonal antibody production.
病毒过滤用于确保生物制药产品（如单克隆抗体）生产中所需的高水平病毒清除率。病毒过滤过程中的通量下降可能是由于由自组装的单体单克隆抗体分子组成的可逆聚集体的形成，特别是在高抗体浓度下。虽然尺寸排阻色谱法通常无法检测到这些可逆聚集体，但动态光散射可用于确定它们的存在。通过使用膜吸附器对进料进行预处理以破坏存在的可逆聚集体，可以使病毒过滤过程中的通量下降最小化。可逆聚集体的形成高度依赖于单克隆抗体和进料条件。对于此处研究的pH值，使用疏水相互作用膜吸附器对进料进行预处理在最小化病毒过滤过程中的通量下降方面最为有效。如果单克隆抗体和膜带相反电荷，离子交换膜也可能有效。因此，与疏水相互作用膜吸附器相比，离子交换膜吸附器的有效性对溶液pH的依赖性要大得多。基于尺寸的预过滤被发现对破坏这些可逆聚集体无效。这些结果有助于指导开发更有效的单克隆抗体生产病毒过滤工艺。
