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Integrated continuous biomanufacturing on pilot scale for acid-sensitive monoclonal antibodies

Schwarz, Hubert ; Gomis-Fons, Joaquín LU ; Isaksson, Madelène LU ; Scheffel, Julia ; Andersson, Niklas LU orcid ; Andersson, Andreas ; Castan, Andreas ; Solbrand, Anita ; Hober, Sophia and Nilsson, Bernt LU , et al. (2022) In Biotechnology and Bioengineering 119(8). p.2152-2166
Abstract

In this study, we demonstrated the first, to our knowledge, integrated continuous bioprocess (ICB) designed for the production of acid-sensitive monoclonal antibodies, prone to aggregate at low pH, on pilot scale. A high cell density perfusion culture, stably maintained at 100 × 106 cells/ml, was integrated with the downstream process, consisting of a capture step with the recently developed Protein A ligand, ZCa; a solvent/detergent-based virus inactivation; and two ion-exchange chromatography steps. The use of a mild pH in the downstream process makes this ICB suitable for the purification of acid-sensitive monoclonal antibodies. Integration and automation of the downstream process were achieved using the Orbit... (More)

In this study, we demonstrated the first, to our knowledge, integrated continuous bioprocess (ICB) designed for the production of acid-sensitive monoclonal antibodies, prone to aggregate at low pH, on pilot scale. A high cell density perfusion culture, stably maintained at 100 × 106 cells/ml, was integrated with the downstream process, consisting of a capture step with the recently developed Protein A ligand, ZCa; a solvent/detergent-based virus inactivation; and two ion-exchange chromatography steps. The use of a mild pH in the downstream process makes this ICB suitable for the purification of acid-sensitive monoclonal antibodies. Integration and automation of the downstream process were achieved using the Orbit software, and the same equipment and control system were used in initial small-scale trials and the pilot-scale downstream process. High recovery yields of around 90% and a productivity close to 1 g purified antibody/L/day were achieved, with a stable glycosylation pattern and efficient removal of impurities, such as host cell proteins and DNA. Finally, negligible levels of antibody aggregates were detected owing to the mild conditions used throughout the process. The present work paves the way for future industrial-scale integrated continuous biomanufacturing of all types of antibodies, regardless of acid stability.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antibody aggregation, antibody manufacturing, Chinese Hamster Ovary cells, continuous chromatography, integrated continuous bioprocess, perfusion culture, Z ligand
in
Biotechnology and Bioengineering
volume
119
issue
8
pages
15 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:35470430
  • scopus:85129383183
ISSN
1097-0290
DOI
10.1002/bit.28120
language
English
LU publication?
yes
id
612906a2-8803-4ad4-8b77-64855c930d52
date added to LUP
2022-02-14 09:41:42
date last changed
2024-04-18 11:59:17
@article{612906a2-8803-4ad4-8b77-64855c930d52,
  abstract     = {{<p>In this study, we demonstrated the first, to our knowledge, integrated continuous bioprocess (ICB) designed for the production of acid-sensitive monoclonal antibodies, prone to aggregate at low pH, on pilot scale. A high cell density perfusion culture, stably maintained at 100 × 10<sup>6</sup> cells/ml, was integrated with the downstream process, consisting of a capture step with the recently developed Protein A ligand, Z<sub>Ca</sub>; a solvent/detergent-based virus inactivation; and two ion-exchange chromatography steps. The use of a mild pH in the downstream process makes this ICB suitable for the purification of acid-sensitive monoclonal antibodies. Integration and automation of the downstream process were achieved using the Orbit software, and the same equipment and control system were used in initial small-scale trials and the pilot-scale downstream process. High recovery yields of around 90% and a productivity close to 1 g purified antibody/L/day were achieved, with a stable glycosylation pattern and efficient removal of impurities, such as host cell proteins and DNA. Finally, negligible levels of antibody aggregates were detected owing to the mild conditions used throughout the process. The present work paves the way for future industrial-scale integrated continuous biomanufacturing of all types of antibodies, regardless of acid stability.</p>}},
  author       = {{Schwarz, Hubert and Gomis-Fons, Joaquín and Isaksson, Madelène and Scheffel, Julia and Andersson, Niklas and Andersson, Andreas and Castan, Andreas and Solbrand, Anita and Hober, Sophia and Nilsson, Bernt and Chotteau, Veronique}},
  issn         = {{1097-0290}},
  keywords     = {{antibody aggregation; antibody manufacturing; Chinese Hamster Ovary cells; continuous chromatography; integrated continuous bioprocess; perfusion culture; Z ligand}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{2152--2166}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Biotechnology and Bioengineering}},
  title        = {{Integrated continuous biomanufacturing on pilot scale for acid-sensitive monoclonal antibodies}},
  url          = {{http://dx.doi.org/10.1002/bit.28120}},
  doi          = {{10.1002/bit.28120}},
  volume       = {{119}},
  year         = {{2022}},
}