The rapidly developing antibody market poses challenges to the production cost and efficiency, which can be addressed through continuous process. However, a hurdle of high capital investment remains a concern especially for the company with existing fed-batch capacity. This study proposes a straightforward approach to convert existing batch production suites into continuous ones using membrane-based technology. A conceptual validation was conducted at a 100 L pilot scale, and a head-to-head comparison was carried out. The results demonstrated that Protein A membrane chromatography could achieve a productivity 6.3 times higher than that of periodic counter-current chromatography (PCC), without requiring the purchase of any dedicated equipment. Using Q membrane, compared with traditional column anion exchange chromatography, can achieve a 16-fold increase in load capacity and a 25-fold increase in productivity. Finally, VF-UF/DF (Virus Filtration-Ultrafiltration/diafiltration) linkage process was designed, resulting in a 20% reduction in process time. During the 23-day upstream perfusion and 15-day downstream processing, the cumulative titer reached 51.0 g/L, with an 83.1% yield in downstream processing. With downstream process time shortening from 4 to 1.5 days, the process capacity could be improved by 8 times using the existing batch production suites and the same facility area. PATs, including ultra-performance liquid chromatography, Raman spectroscopy, FlowVPX, and an inline turbidity meter, were integrated to monitor process CQAs (Critical Quality Attributes): monomer purity, protein concentration, and turbidity, to enable efficient process control in the future.
Fang et al. (Wed,) studied this question.
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