A straightforward approach for converting existing batch production to an integrated continuous manufacturing suite...

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.