An integrated continuous downstream process with real-time control: A case study with periodic countercurrent chromatography and continuous virus inactivation

Anton Löfgren, Joaquin Gomis-Fons, Niklas Andersson, Bernt Nilsson, Lotta Berghard, Christine Lagerquist Hägglund

Research output: Working paper/PreprintPreprint (in preprint archive)

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%.
Original languageEnglish
PublisherAuthorea
Number of pages18
DOIs
Publication statusPublished - 2021 Jan 12

Subject classification (UKÄ)

  • Chemical Engineering

Keywords

  • CONTINUOUS VIRUS INACTIVATION
  • INTEGRATED CONTINUOUS DOWNSTREAM
  • PERIODIC COUNTERCURRENT CHROMATOGRAPHY
  • PROCESS ANALYTICAL TECHNOLOGY
  • REAL-TIME CONTROL

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