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An integrated continuous downstream process with real‐time control: A case study with periodic countercurrent chromatography and continuous virus inactivation
Author(s) -
Löfgren Anton,
GomisFons Joaquín,
Andersson Niklas,
Nilsson Bernt,
Berghard Lotta,
Lagerquist Hägglund Christine
Publication year - 2021
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27681
Subject(s) - downstream processing , controller (irrigation) , process (computing) , process engineering , countercurrent exchange , process control , continuous production , downstream (manufacturing) , batch processing , flexibility (engineering) , computer science , chromatography , chemistry , mathematics , engineering , chemical engineering , physics , thermodynamics , operations management , statistics , agronomy , biology , programming language , operating system
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 multiproduct and multipurpose 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 h, 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%.