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

Journal of Biotechnology
Daniel BaurMassimo Morbidelli

Abstract

Effect 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 on the order of 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 brea...Continue Reading

Citations

May 8, 2019·Biotechnology and Bioengineering·James AngeloZhengjian Li
Jun 10, 2020·Annual Review of Chemical and Biomolecular Engineering·Vijesh Kumar, Abraham M Lenhoff
Jan 11, 2020·Frontiers in Bioengineering and Biotechnology·Nagesh K Tripathi, Ambuj Shrivastava
Feb 6, 2020·Biotechnology and Bioengineering·Fabian FeidlMassimo Morbidelli
Jan 15, 2021·Journal of Chromatography. a·Dong-Qiang LinShan-Jing Yao
Feb 28, 2021·Biotechnology and Bioengineering·Alex Brinkmann, Sanaa Elouafiq

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