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Model-based design and control of a small-scale integrated continuous end-to-end mAb platform

Gomis-Fons, Joaquín LU ; Schwarz, Hubert ; Zhang, Liang ; Andersson, Niklas LU ; Nilsson, Bernt LU ; Castan, Andreas ; Solbrand, Anita ; Stevenson, Joanne and Chotteau, Véronique (2020) In Biotechnology Progress
Abstract

A continuous integrated bioprocess available from the earliest stages of process development allows for an easier, more efficient and faster development and characterization of an integrated process as well as production of small-scale drug candidates. The process presented in this article is a proof-of-concept of a continuous end-to-end monoclonal antibody production platform at a very small scale based on a 200 ml alternating tangential flow filtration perfusion bioreactor, integrated with the purification process with a model-based design and control. The downstream process, consisting of a periodic twin-column protein A capture, a virus inactivation, a CEX column and an AEX column, was compactly implemented in a single... (More)

A continuous integrated bioprocess available from the earliest stages of process development allows for an easier, more efficient and faster development and characterization of an integrated process as well as production of small-scale drug candidates. The process presented in this article is a proof-of-concept of a continuous end-to-end monoclonal antibody production platform at a very small scale based on a 200 ml alternating tangential flow filtration perfusion bioreactor, integrated with the purification process with a model-based design and control. The downstream process, consisting of a periodic twin-column protein A capture, a virus inactivation, a CEX column and an AEX column, was compactly implemented in a single chromatography system, with a purification time of less than 4 hr. Monoclonal antibodies were produced for 17 days in a high cell density perfusion culture of CHO cells with titers up to 1.0 mg/ml. A digital twin of the downstream process was created by modelling all the chromatography steps. These models were used for real-time decision making by the implementation of control strategies to automatize and optimize the operation of the process. A consistent glycosylation pattern of the purified product was ensured by the steady state operation of the process. Regarding the removal of impurities, at least a 4-log reduction in the HCP levels was achieved. The recovery yield was up to 60%, and a maximum productivity of 0.8 mg/ml/day of purified product was obtained.

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author
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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
end-to-end continuous bioprocessing, monoclonal antibody, perfusion bioreactor, process integration, process modelling
in
Biotechnology Progress
article number
e2995
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:32233078
  • scopus:85082930241
ISSN
8756-7938
DOI
10.1002/btpr.2995
language
English
LU publication?
yes
id
0647023e-19e9-42af-9a68-6a4cc6b72238
date added to LUP
2020-05-08 13:57:12
date last changed
2020-10-20 04:17:54
@article{0647023e-19e9-42af-9a68-6a4cc6b72238,
  abstract     = {<p>A continuous integrated bioprocess available from the earliest stages of process development allows for an easier, more efficient and faster development and characterization of an integrated process as well as production of small-scale drug candidates. The process presented in this article is a proof-of-concept of a continuous end-to-end monoclonal antibody production platform at a very small scale based on a 200 ml alternating tangential flow filtration perfusion bioreactor, integrated with the purification process with a model-based design and control. The downstream process, consisting of a periodic twin-column protein A capture, a virus inactivation, a CEX column and an AEX column, was compactly implemented in a single chromatography system, with a purification time of less than 4 hr. Monoclonal antibodies were produced for 17 days in a high cell density perfusion culture of CHO cells with titers up to 1.0 mg/ml. A digital twin of the downstream process was created by modelling all the chromatography steps. These models were used for real-time decision making by the implementation of control strategies to automatize and optimize the operation of the process. A consistent glycosylation pattern of the purified product was ensured by the steady state operation of the process. Regarding the removal of impurities, at least a 4-log reduction in the HCP levels was achieved. The recovery yield was up to 60%, and a maximum productivity of 0.8 mg/ml/day of purified product was obtained.</p>},
  author       = {Gomis-Fons, Joaquín and Schwarz, Hubert and Zhang, Liang and Andersson, Niklas and Nilsson, Bernt and Castan, Andreas and Solbrand, Anita and Stevenson, Joanne and Chotteau, Véronique},
  issn         = {8756-7938},
  language     = {eng},
  month        = {03},
  publisher    = {The American Chemical Society (ACS)},
  series       = {Biotechnology Progress},
  title        = {Model-based design and control of a small-scale integrated continuous end-to-end mAb platform},
  url          = {http://dx.doi.org/10.1002/btpr.2995},
  doi          = {10.1002/btpr.2995},
  year         = {2020},
}