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Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system
Author(s) -
Fedorenko Dmitriy,
Dutta Amit K.,
Tan Jasmine,
Walko Jonathan,
Brower Mark,
Pinto Nuno D. S.,
Zydney Andrew L.,
Shinkazh Oleg
Publication year - 2020
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27232
Subject(s) - chromatography , bioprocess , countercurrent exchange , size exclusion chromatography , chemistry , particle size , elution , diafiltration , filtration (mathematics) , countercurrent chromatography , cross flow filtration , particle (ecology) , agarose , column chromatography , chemical engineering , mathematics , biochemistry , physics , statistics , oceanography , membrane , geology , engineering , thermodynamics , enzyme , microfiltration
Continuous countercurrent tangential chromatography (CCTC) enables steady‐state continuous bioprocessing with low‐pressure operation and high productivity. CCTC has been applied to initial capture of monoclonal antibodies (mAb) from clarified cell culture harvest and postcapture polishing of mAb; however, these studies were performed with commercial chromatography resins designed for conventional column chromatography. In this study, a small particle size prototype agarose resin (20–25 µm ) with lower cross‐linking was co‐developed with industrial partner Purolite and tested with CCTC. Due to increased binding capacity and faster kinetics, the resulting CCTC process showed more than a 2X increase in productivity, and a 2X reduction in buffer consumption over commercial protein A resins used in previous CCTC studies, as well as more than a 10X productivity increase versus conventional column operation. Single‐pass tangential flow filtration was integrated with the CCTC system, enabling simple control of eluate concentration. A scale‐up exercise was conducted to provide a quantitative comparison of CCTC and batch column chromatography. These results clearly demonstrate opportunities for using otherwise unpackable soft small particle size resins with CCTC as the core of a continuous bioprocessing platform.