Ongoing efforts in the biopharmaceutical industry to enhance productivity and reduce manufacturing costs include development of intensified, linked, and/or continuous processes. One approach to improve productivity and process economics of the polishing step (i.e., anion exchange chromatography) is to preconcentrate the product intermediate using a single‐pass tangential flow filtration step before loading on the resin. This intensification of the polishing step consequently leads to changes in product intermediate concentration for subsequent virus filtration operations, potentially impacting filter performance and methods for evaluating viral clearance. The filtrate flux performance of a virus filtration operation was evaluated with monoclonal antibody (mAb) solutions of varying concentrations. These data were used to evaluate the effect on filter sizing for a hypothetical mAb perfusion process. The optimum mAb concentration to minimize the area of the virus filter was a function of the filtration step duration and reflected the competing effects of increasing concentration and decreasing volumetric flux on the membrane productivity. mAb solutions at high and low concentrations were used to evaluate viral clearance with extended filtration times (e.g., 24–72 h) simulating continuous processing conditions. Modifications to more traditional filtration viral clearance study methods were required to avoid experimental artifacts associated with the extended filtration time. No virus passage through the filter was observed under these conditions, similar to previous results for batch processes. These data demonstrate the feasibility of obtaining effective virus removal even when mAb concentration and filtrations times are increased by up to an order of magnitude from current common practices.

中文翻译：

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调整病毒过滤以实现强化和连续的单克隆抗体处理

生物制药行业为提高生产力和降低制造成本而进行的持续努力包括开发强化、链接和/或连续工艺。提高抛光步骤（即阴离子交换色谱法）的生产率和工艺经济性的一种方法是在加载到树脂上之前使用单程切向流过滤步骤预浓缩产物中间体。因此，精制步骤的强化会导致后续病毒过滤操作的产品中间浓度发生变化，从而可能影响过滤器性能和评估病毒清除率的方法。使用不同浓度的单克隆抗体 (mAb) 溶液评估病毒过滤操作的滤液通量性能。这些数据用于评估假设 mAb 灌注过程对过滤器尺寸的影响。使病毒过滤器面积最小化的最佳 mAb 浓度是过滤步骤持续时间的函数，反映了增加浓度和降低体积通量对膜生产率的竞争效应。使用高浓度和低浓度的 mAb 溶液来评估病毒清除率以及延长过滤时间（例如 24-72 小时）模拟连续处理条件。需要对更传统的过滤病毒清除研究方法进行修改，以避免与延长过滤时间相关的实验伪影。在这些条件下，没有观察到病毒通过过滤器，这与之前批处理的结果相似。