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

被引:69
作者
Baur, Daniel [1 ]
Angarita, Monica [1 ]
Mueller-Spaeth, Thomas [1 ,2 ]
Morbidelli, Massimo [1 ]
机构
[1] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, CH-8093 Zurich, Switzerland
[2] ChromaCon AG, Zurich, Switzerland
关键词
Model based optimization; Monoclonal antibody; Periodic counter-current chromatography; Protein A affinity chromatography; Sequential capture; GRADIENT PURIFICATION MCSGP; ION-EXCHANGE CHROMATOGRAPHY; ANTIBODY-CAPTURE; MASS-TRANSFER; ADSORPTION; OPTIMIZATION; SEPARATIONS; SIMULATION; SORBENTS; MIXTURE;
D O I
10.1002/biot.201500223
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:135 / 145
页数:11
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