Harmonizing unit operations in the downstream process of monoclonal antibodies (mAbs) has a high potential to overcome throughput limitations and reduce manufacturing costs. This study proposes a streamlined clarification and capture (S‐CC) process concept for the continuous processing of cell broth harvested from a connected bioreactor. The process was realized with a fluidized bed centrifuge connected to depth and sterile filters, a surge tank, and a multi‐column chromatography (MCC) unit. The MCC unit was operated in the rapid cycling simulated moving bed (RC‐BioSMB) mode with five convective diffusive membrane adsorbers (MAs). A control strategy and the surge tank were used to adjust the loading flow rate of the MCC unit. The mAb was recovered with a total process yield of 90%, with high removal of the process‐related impurities HCP (2.1 LRV) and DNA (2.9 LRV). Moreover, the S‐CC process productivity of 4.2 g h−1 was up to 5.3 times higher than for comparable, hypothetical batch MA processes. In addition, the buffer consumption of the capture step could be reduced from 2.0 L g−1 in batch mode to 1.2 L g−1 in the RC‐BioSMB mode. These results demonstrate the high potential of streamlined interconnected unit operations to improve the overall mAb downstream process performance.

中文翻译：

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使用流化床离心法和多柱层析（含膜吸附器）简化单克隆抗体的澄清和捕获工艺


协调单克隆抗体 （mAb） 下游工艺中的单元操作具有克服通量限制和降低生产成本的巨大潜力。本研究提出了一种简化的澄清和捕获 （S-CC） 工艺概念，用于连续处理从连接的生物反应器中收获的细胞液。该工艺是通过连接到深层和无菌过滤器的流化床离心机、缓冲罐和多柱色谱 （MCC） 装置实现的。MCC 装置在快速循环模拟移动床 （RC-BioSMB） 模式下运行，配备 5 个对流扩散膜吸附器 （MA）。使用控制策略和缓冲罐来调节 MCC 装置的负载流量。回收 mAb 后，总工艺产量为 90%，去除了工艺相关杂质 HCP （2.1 LRV） 和 DNA （2.9 LRV）。此外，4.2 g h-1 的 S-CC 工艺生产率比可比的假设批量 MA 工艺高 5.3 倍。此外，捕获步骤的缓冲液消耗量可以从批量模式下的 2.0 L g-1 降低到 RC-BioSMB 模式下的 1.2 L g-1。这些结果表明，简化的互连单元操作在提高 mAb 下游工艺的整体性能方面具有很大的潜力。