title: Optimal model-based design of the twin-column CaptureSMB process improves capacity utilization and productivity in protein A affinity capture.
abstract: 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.
authors: Department for Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors: Daniel
authors: D
authors: Baur
authors: Department for Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors: Monica
authors: M
authors: Angarita
authors: Department for Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.|ChromaCon AG, Zurich, Switzerland.
authors: Thomas
authors: T
authors: Müller-Späth
authors: Department for Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland. massimo.morbidelli@chem.ethz.ch.
authors: Massimo
authors: M
authors: Morbidelli
mesh_terms: D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000302:isolation & purification*; D061249:Batch Cell Culture Techniques / Q000379:methods; D002846:Chromatography, Affinity / Q000295:instrumentation* / Q000379:methods; D008956:Models, Chemical; D013205:Staphylococcal Protein A / Q000737:chemistry* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D013205:Staphylococcal Protein A
keywords: Model based optimization; Monoclonal antibody; Periodic counter-current chromatography; Protein A affinity chromatography; Sequential capture