Model assisted comparison of Protein A resins and multi-column chromatography for capture processes

Publication date: Available online 27 August 2018Source: Journal of BiotechnologyAuthor(s): Daniel Baur, James M. Angelo, Srinivas Chollangi, Xuankuo Xu, Thomas Müller-Späth, Na Zhang, Sanchayita Ghose, Zheng Jian Li, Massimo MorbidelliAbstractEffect of particle size (85μm vs. 50μm) on the performance of continuous capture chromatography using Protein A affinity was evaluated in combination with varied feed titers, loading flow rates and target breakthrough using a Design of Experiments (DoE) approach. In comparison to previous studies, higher cell culture titers in the order 5 - 15 g/L relevant to current high productivity industrial cell lines were evaluated. Further, three modes of capture continuous chromatography were included in the DoE: single column batch, 2-column CaptureSMB and 4-column periodic counter-current chromatography (PCC). The breakthrough percentage at the outlet of the first column being loaded showed the most significant impact on process performance, confirming the advantage of multi-column over batch chromatography processes. Out of the two resins, the one with smaller particle size displayed significantly better performance. To verify and generalize these results, a shrinking core model for protein A chromatography has been developed and validated. The model was used to optimize the processes with respect to capacity utilization (load per cycle) and productivity (load per time). The smaller particle size resin (50μm) produced steeper breakthro...

Source: Journal of Biotechnology - August 28, 2018 Category: Biotechnology Source Type: research