An integrated continuous downstream process with real-time control: A case study with periodic countercurrent chromatography and continuous virus inactivation
(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:
https://lup.lub.lu.se/record/3ae4b6cb-bce9-4917-84fb-243ef8e27e49
- author
- Löfgren, Anton LU ; Gomis-Fons, Joaquin LU ; Andersson, Niklas LU ; Nilsson, Bernt LU ; Berghard, Lotta and Lagerquist Hägglund, Christine
- organization
- publishing date
- 2021-01-12
- 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
- 2021-12-08 15:36:29
@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}}, }