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

Löfgren, Anton LU ; Gomis-Fons, Joaquin LU ; Andersson, Niklas LU ; Nilsson, Bernt LU ; Berghard, Lotta and Lagerquist Hägglund, Christine (2021)
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.... (More)
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%. (Less)
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publication status
published
subject
keywords
CONTINUOUS VIRUS INACTIVATION, INTEGRATED CONTINUOUS DOWNSTREAM, PERIODIC COUNTERCURRENT CHROMATOGRAPHY, PROCESS ANALYTICAL TECHNOLOGY, REAL-TIME CONTROL
pages
18 pages
DOI
10.22541/au.160029924.40393430
language
English
LU publication?
yes
id
3ae4b6cb-bce9-4917-84fb-243ef8e27e49
date added to LUP
2021-03-09 10:12:00
date last changed
2021-03-11 11:10:59
@misc{3ae4b6cb-bce9-4917-84fb-243ef8e27e49,
  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%.},
  author       = {Löfgren, Anton and Gomis-Fons, Joaquin and Andersson, Niklas and Nilsson, Bernt and Berghard, Lotta and Lagerquist Hägglund, Christine},
  language     = {eng},
  month        = {01},
  title        = {An integrated continuous downstream process with real-time control: A case study with periodic countercurrent chromatography and continuous virus inactivation},
  url          = {http://dx.doi.org/10.22541/au.160029924.40393430},
  doi          = {10.22541/au.160029924.40393430},
  year         = {2021},
}