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)
JournalBiotechnology and bioengineering
DOIs
StateAccepted/In press - Jan 1 2019

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Countercurrent Distribution
Staphylococcal Protein A
Chromatography
Antibodies
Resins
Proteins
Column chromatography
Monoclonal antibodies
Productivity
Particle Size
Monoclonal Antibodies
Particle size
Sepharose
Polishing
Cell culture
Buffers
Cell Culture Techniques
Pressure

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Fedorenko, D., Dutta, A. K., Tan, J., Walko, J., Brower, M., Pinto, N. D. S., ... Shinkazh, O. (Accepted/In press). Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system. Biotechnology and bioengineering. https://doi.org/10.1002/bit.27232
Fedorenko, Dmitriy ; Dutta, Amit K. ; Tan, Jasmine ; Walko, Jonathan ; Brower, Mark ; Pinto, Nuno D.S. ; Zydney, Andrew L. ; Shinkazh, Oleg. / Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system. In: Biotechnology and bioengineering. 2019.
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Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system. / Fedorenko, Dmitriy; Dutta, Amit K.; Tan, Jasmine; Walko, Jonathan; Brower, Mark; Pinto, Nuno D.S.; Zydney, Andrew L.; Shinkazh, Oleg.

In: Biotechnology and bioengineering, 01.01.2019.

Research output: Contribution to journalArticle

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