Optimal model‐based design of the twin‐column CaptureSMB process improves capacity utilization and productivity in protein A affinity capture

Multi‐column chromatographic processes have recently been developed for protein A affinity chromatography to efficiently capture monoclonal antibodies from cell culture supernatant. In this work, the novel twin‐column CaptureSMB process was compared to a batch capture process with dual loading flow rate to identify performance gains. As a case study, the isolation of a monoclonal antibody with the Amsphere JWT‐203 protein A resin was investigated. Using model based optimization, both processes were optimized and compared over a wide range of operating conditions. A trade‐off between productivity and capacity utilization was found, and the resulting pareto‐curves showed that CaptureSMB dominates batch, except at very low productivity values. With a feed titer of 1.2 mg mL −1 , CaptureSMB could reach a productivity of up to 19.5 mg mL −1 h −1 experimentally, while maintaining relatively high capacity utilization of 63.8%. On the other hand, at maximum capacity utilization of 95.5%, a productivity of 10.2 mg mL −1 h −1 could be reached. This corresponds to a performance improvement with respect batch operation of about 25% in capacity utilization and 40% in productivity, for given yield and purity. CaptureSMB therefore offers a greatly increased performance over batch capture.