Side-by-side comparability of batch and continuous downstream for the production of monoclonal antibodies.
DSP
continuous processing
mAb
side-by-side comparability
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
08
07
2019
revised:
08
11
2019
accepted:
06
01
2020
pubmed:
14
1
2020
medline:
12
2
2021
entrez:
14
1
2020
Statut:
ppublish
Résumé
Continuous processing is the future production method for monoclonal antibodies (mAbs). A fully continuous, fully automated downstream process based on disposable equipment was developed and implemented inside the MoBiDiK pilot plant. However, a study evaluating the comparability between batch and continuous processing based on product quality attributes was not conducted before. The work presented fills this gap comparing both process modes experimentally by purifying the same harvest material (side-by-side comparability). Samples were drawn at different time points and positions in the process for batch and continuous mode. Product quality attributes, product-related impurities, as well as process-related impurities were determined. The resulting polished material was processed to drug substance and further evaluated regarding storage stability and degradation behavior. The in-process control data from the continuous process showed the high degree of accuracy in providing relevant process parameters such as pH, conductivity, and protein concentration during the entire process duration. Minor differences between batch and continuous samples are expected as different processing conditions are unavoidable due to the different nature of batch and continuous processing. All tests revealed no significant differences in the intermediates and comparability in the drug substance between the samples of both process modes. The stability study of the final product also showed no differences in the stability profile during storage and forced degradation. Finally, online data analysis is presented as a powerful tool for online-monitoring of chromatography columns during continuous processing.
Substances chimiques
Antibodies, Monoclonal
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1024-1036Subventions
Organisme : German Federal State North Rhine-Westphalia
ID : 005-1010-0009
Pays : International
Organisme : European Regional Development Fund
ID : 005-1010-0009
Pays : International
Organisme : Bundesministerium für Bildung und Forschung
ID : 031A616M
Pays : International
Informations de copyright
© 2020 Wiley Periodicals, Inc.
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