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An integrated continuous downstream process with real-time control: A case study with periodic countercurrent chromatography and continuous virus inactivation
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  • Anton Löfgren,
  • Joaquin Gomis-Fons,
  • Niklas Andersson,
  • Bernt Nilsson,
  • Lotta Berghard,
  • Chistine Lagerquist Hägglund
Anton Löfgren
Lunds Universitet Tekniska Hogskola
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Joaquin Gomis-Fons
Lunds Universitet Tekniska Hogskola
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Niklas Andersson
Lunds Universitet Tekniska Hogskola
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Bernt Nilsson
Lund University
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Lotta Berghard
Swedish Orphan Biovitrum AB
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Chistine Lagerquist Hägglund
Swedish Orphan Biovitrum AB
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Abstract

Integrated continuous downstream processes with process analytical technology offer a promising opportunity to reduce production costs and increase process flexibility and adaptability. In this case study, an integrated continuous process was used to purify a recombinant protein on laboratory scale in a two-system setup that can be used as a general downstream setup offering multi-product and multi-purpose manufacturing capabilities. The process consisted of continuous solvent/detergent virus inactivation followed by periodic countercurrent chromatography in the capture step, and a final chromatographic polishing step. A real-time controller was implemented to ensure stable operation by adapting the downstream process to external changes. A concentration disturbance was introduced to test the controller. After the disturbance was applied, the product output recovered within 6 hours, showing the effectiveness of the controller. In a comparison of the process with and without the controller, the product output per cycle increased by 27%, the resin utilization increased from 71.4% to 87.9%, and the specific buffer consumption was decreased by 21% with the controller, while maintaining a similar yield and purity as in the process without the disturbance. In addition, the integrated continuous process outperformed the batch process, increasing the productivity by 95% and the yield by 28%.

Peer review status:POSTED

16 Sep 2020Submitted to Biotechnology and Bioengineering
16 Sep 2020Assigned to Editor
16 Sep 2020Submission Checks Completed