Enhanced filtration performance usingfeed-and-bleedconfiguration for purification of antibody precipitates
Enhanced filtration performance usingfeed-and-bleedconfiguration for purification of antibody precipitates
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DOI：
10.1002/btpr.3082
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发表时间：
2020-09-28
影响因子：
2.9
通讯作者：
Zydney, Andrew L.
中科院分区：
文献类型：
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作者：
Li, Zhao;Chen, Ting-Hsi;Zydney, Andrew L.
沉淀法可用于单抗的初步纯化，通过切向流微滤去除渗透液中的可溶性宿主细胞蛋白。这项研究的目的是研究使用进料和排气结构来提高中空纤维组件中的有效转化率(渗透液与进料流量的比率)，以实现更有效的沉淀物洗涤。用10 mM氯化锌和7wt%聚乙二醇形成的人血清免疫球蛋白G(Ig G)沉淀物进行实验。临界通量作为剪切速率和免疫球蛋白浓度的函数进行了评估，由此得到的相关性用于预测在最小污染的情况下单程转化率可达90%的条件。启动和稳态性能的实验数据与模型计算结果吻合较好。这些结果被用来分析增强的连续沉淀-微滤过程的性能，该过程使用进料和放气配置来初始捕获/纯化单抗产品。
Precipitation can be used for the initial purification of monoclonal antibodies (mAbs), with the soluble host cell proteins removed in the permeate by tangential flow microfiltration. The objective of this study was to examine the use of a feed-and-bleed configuration to increase the effective conversion (ratio of permeate to feed flow rates) in the hollow fiber module to enable more effective washing of the precipitate. Experiments were performed using human serum Immunoglobulin G (IgG) precipitates formed with 10 mM zinc chloride and 7 wt% polyethylene glycol. The critical flux was evaluated as a function of the shear rate and IgG concentration, with the resulting correlation used to predict conditions that can achieve 90% conversion in a single pass with minimal fouling. Experimental data for both the start-up and steady-state performance are in good agreement with model calculations. These results were used to analyze the performance of an enhanced continuous precipitation-microfiltration process using the feed-and-bleed configuration for the initial capture / purification of a mAb product.