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

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 post capture 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 3X 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 vs. conventional column operation. Single Pass Tangential Flow Filtration (SPTFF) 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.



Work Title Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system
Open Access
  1. Dmitriy Fedorenko
  2. Amit K. Dutta
  3. Jasmine Tan
  4. Jonathan Walko
  5. Mark Brower
  6. Nuno D. Pinto
  7. Andrew Zydney
  8. Oleg Shinkazh
  1. Antibody
  2. Continuous chromatography
  3. Protein A
  4. Purification
  5. Single‐use
License In Copyright (Rights Reserved)
Work Type Article
  1. Biotechnology and Bioengineering
Publication Date November 30, 2019
Publisher Identifier (DOI)
Deposited January 23, 2023




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Work History

Version 1

  • Created
  • Added Improved_protein_A_CCTC.pdf
  • Added Creator Dmitriy Fedorenko
  • Added Creator Amit K. Dutta
  • Added Creator Jasmine Tan
  • Added Creator Jonathan Walko
  • Added Creator Mark Brower
  • Added Creator Nuno D. Pinto
  • Added Creator Andrew Zydney
  • Added Creator Oleg Shinkazh
  • Published
  • Updated Keyword, Publication Date Show Changes
    • Antibody, Continuous chromatography, Protein A, Purification, Single‐use
    Publication Date
    • 2020-03-01
    • 2019-11-30