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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 orcid ; Gomis-Fons, Joaquín LU ; Andersson, Niklas LU orcid ; Nilsson, Bernt LU orcid ; Berghard, Lotta and Lagerquist Hägglund, Christine (2021) In Biotechnology and Bioengineering 118(4). p.1664-1676
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 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.... (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 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%.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
continuous virus inactivation, integrated continuous downstream, periodic countercurrent chromatography, process analytical technology, real-time control
in
Biotechnology and Bioengineering
volume
118
issue
4
pages
13 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:33459355
  • scopus:85100335177
ISSN
0006-3592
DOI
10.1002/bit.27681
language
English
LU publication?
yes
id
b568d12a-4d17-4af3-87e6-2a59a163db2e
date added to LUP
2021-12-08 15:38:14
date last changed
2025-02-09 22:07:02
@article{b568d12a-4d17-4af3-87e6-2a59a163db2e,
  abstract     = {{<p>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%.</p>}},
  author       = {{Löfgren, Anton and Gomis-Fons, Joaquín and Andersson, Niklas and Nilsson, Bernt and Berghard, Lotta and Lagerquist Hägglund, Christine}},
  issn         = {{0006-3592}},
  keywords     = {{continuous virus inactivation; integrated continuous downstream; periodic countercurrent chromatography; process analytical technology; real-time control}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{1664--1676}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Biotechnology and Bioengineering}},
  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/10.1002/bit.27681}},
  doi          = {{10.1002/bit.27681}},
  volume       = {{118}},
  year         = {{2021}},
}