Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system

Dmitriy Fedorenko, Amit K. Dutta, Jasmine Tan, Jonathan Walko, Mark Brower, Nuno D.S. Pinto, Andrew L. Zydney, Oleg Shinkazh

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)646-653
Number of pages8
JournalBiotechnology and bioengineering
Volume117
Issue number3
DOIs
StatePublished - Mar 1 2020

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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