Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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, Joaquin LU ; Andersson, Niklas LU orcid ; Nilsson, Bernt LU orcid ; 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)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Working paper/Preprint
publication status
published
subject
keywords
CONTINUOUS VIRUS INACTIVATION, INTEGRATED CONTINUOUS DOWNSTREAM, PERIODIC COUNTERCURRENT CHROMATOGRAPHY, PROCESS ANALYTICAL TECHNOLOGY, REAL-TIME CONTROL
pages
18 pages
publisher
Authorea
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
2025-04-04 15:09:53
@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}},
  keywords     = {{CONTINUOUS VIRUS INACTIVATION; INTEGRATED CONTINUOUS DOWNSTREAM; PERIODIC COUNTERCURRENT CHROMATOGRAPHY; PROCESS ANALYTICAL TECHNOLOGY; REAL-TIME CONTROL}},
  language     = {{eng}},
  month        = {{01}},
  note         = {{Preprint}},
  publisher    = {{Authorea}},
  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}},
}