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面向工业放大评估的单抗除病毒过滤中预过滤器类型对载量与通量衰减的影响

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  • 1上海生物制品研究所有限责任公司抗体中心,上海  200051;2默克化工技术(上海)有限公司工艺解决方案,上海 200040

网络出版日期: 2026-08-11

Evaluation of different prefilters on throughput and flux decline in industrial scale-up monoclonal antibody virus filtration

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  • 1Antibody Center, Shanghai Institute of Biological Products Co., Ltd.,Shanghai 200051,China;2Process Solutions,Merck Chemicals Technology (Shanghai) Co., Ltd.,Shanghai 200040,China

Online published: 2026-08-11

摘要

目的 在工业放大评估背景下,比较不同预过滤器与除病毒滤器Viresolve® Pro(简称Vpro)串联时对单克隆抗体料液过滤载量和通量衰减行为的影响,并评估新鲜料液与冻融料液条件下不同预过滤方案的工艺表现差异,为生产规模除病毒过滤预过滤器的探索性选型提供参考。方法 选取Millistak+® X0HC Media(简称X0HC)、Millistak+® HC Pro X0SP Media(简称X0SP)和Viresolve® Prefilter(简称VPF)3类预过滤器分别与除病毒过滤器Vpro进行串联组合,在恒压条件下开展过滤测试,比较不同组合的过滤载量、通量衰减和基于3 h处理1 000 L料液场景的耗材成本估算;同时结合动态光散射、分子排阻色谱和毛细管凝胶电泳等方法,对新鲜料液与冻融料液的粒径特征及部分质量属性进行分析。结果 在此研究条件下,3种预过滤组合对新鲜料液的过滤表现总体接近,载量均可达约700 L/m²,通量衰减不超过3%。对于冻融料液,标称孔径较小的预过滤器组合(X0HC+Vpro、X0SP+Vpro)表现出更好的载量和通量稳定性,而VPF+Vpro组合通量衰减达77%,实验载量仅约567 L/m²。基于“3 h处理1 000 L料液”场景的耗材成本估算显示,X0HC+Vpro组合的单批次耗材估算成本最低。结论 在此研究体系和实验条件下,合理选择预过滤器类型可能有助于改善病毒过滤通量表现并提高单位膜面积处理能力,为降低工业放大成本、提高工艺稳健性提供参考。

本文引用格式

杨明涛, 李小灵, 何燕娜, 王晖, 孙韬, 尹梦梦, 邱建华 . 面向工业放大评估的单抗除病毒过滤中预过滤器类型对载量与通量衰减的影响[J]. 国际生物制品学杂志, 2026 , 49(4) : 223 -229 . DOI: 10.3760/cma.j.cn311962-20260526-00032

Abstract

Objective To compare effects of different prefilter types in series with virus filter Viresolve® Pro(Vpro) on throughput and flux decline during monoclonal antibody virus filtration in the context of industrial scale-up assessment, and to evaluate differences in process performance among prefiltration schemes under fresh and freeze-thawed feed conditions, so as to provide a reference for the exploratory selection of prefilters for manufacturing-scale virus filtration.Methods Three prefilters, Millistak+® X0HC Media (X0HC), Millistak+® HC Pro X0SP Media (X0SP), and Viresolve® Prefilter (VPF), were evaluated in series with the virus filter Vpro under constant-pressure conditions. Filter throughput, flux decline, and consumable costs for a predefined scenario of processing 1 000 L over 3 h were compared among different filter combinations. In addition, particle size characteristics and selected quality attributes of fresh and freeze-thawed feed materials were analyzed by dynamic light scattering, size exclusion chromatography, and capillary electrophoresis.Results Under the conditions of this study, the three prefilter combinations showed generally comparable performance for fresh feed, with throughputs of approximately 700 L/m² and flux declines of no more than 3%. For freeze-thawed feed, combinations with smaller pore size prefilters (X0HC+Vpro and X0SP+Vpro) showed better throughput and flux stability, whereas the VPF+Vpro combination exhibited a flux decline of up to 77% and an experimental throughput of only approximately 567 L/m². Based on a scenario of processing 1 000 L of feed within 3 h, X0HC+Vpro showed the lowest estimated consumable cost per batch.Conclusion Under the specific product and experimental conditions investigated in this study, appropriate prefilter selection may help improve flux performance and increase throughput per unit membrane area, providing a reference for cost reduction and process robustness enhancement at industrial scale.
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