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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

Corresponding Author:[email protected]

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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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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%.
16 Sep 2020Submitted to Biotechnology and Bioengineering
16 Sep 2020Submission Checks Completed
16 Sep 2020Assigned to Editor
02 Oct 2020Reviewer(s) Assigned
09 Nov 2020Editorial Decision: Revise Minor
09 Nov 2020Review(s) Completed, Editorial Evaluation Pending
19 Nov 20201st Revision Received
20 Nov 2020Submission Checks Completed
20 Nov 2020Assigned to Editor
12 Jan 2021Review(s) Completed, Editorial Evaluation Pending
12 Jan 2021Editorial Decision: Accept