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  4. Comparison of mechanistic and hybrid modeling approaches for characterization of a CHO cultivation process: Requirements, pitfalls and solution paths
 
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Comparison of mechanistic and hybrid modeling approaches for characterization of a CHO cultivation process: Requirements, pitfalls and solution paths

Citation Link: https://doi.org/10.15480/882.4864
Publikationstyp
Journal Article
Date Issued
2023-01
Sprache
English
Author(s)
Bayer, Benjamin  
Duerkop, Mark  
Pörtner, Ralf  orcid-logo
Möller, Johannes  
Institut
Bioprozess- und Biosystemtechnik V-1  
TORE-DOI
10.15480/882.4864
TORE-URI
http://hdl.handle.net/11420/14321
Journal
Biotechnology journal  
Volume
18
Issue
1
Article Number
2200381
Citation
Biotechnology Journal 1 (18): 2200381 (2023-01)
Publisher DOI
10.1002/biot.202200381
Scopus ID
2-s2.0-85142935091
PubMed ID
36382343
Publisher
Wiley-VCH
Despite the advantages of mathematical bioprocess modeling, successful model implementation already starts with experimental planning and accordingly can fail at this early stage. For this study, two different modeling approaches (mechanistic and hybrid) based on a four-dimensional antibody-producing CHO fed-batch process are compared. Overall, 33 experiments are performed in the fractional factorial four-dimensional design space and separated into four different complex data partitions subsequently used for model comparison and evaluation. The mechanistic model demonstrates the advantage of prior knowledge (i.e., known equations) to get informative value relatively independently of the utilized data partition. The hybrid approach displayes a higher data dependency but simultaneously yielded a higher accuracy on all data partitions. Furthermore, our results demonstrate that independent of the chosen modeling framework, a smart selection of only four initial experiments can already yield a very good representation of a full design space independent of the chosen modeling structure. Academic and industry researchers are recommended to pay more attention to experimental planning to maximize the process understanding obtained from mathematical modeling.
Subjects
bioprocess characterization
Chinese hamster ovary cells
design of experiments
machine learning
mechanistic modelling
parameter identification
quality by design
upstream bioprocessing
DDC Class
570: Biowissenschaften, Biologie
Funding(s)
Projekt DEAL  
Funding Organisations
Bundesministerium für Bildung und Forschung (BMBF)  
More Funding Information
Johannes Möller and Ralf Pörtner acknowledge partial funding by the German Federal Ministry of Education and Research (BMBF, Grant 031B0577A-C).
Publication version
publishedVersion
Lizenz
https://creativecommons.org/licenses/by-nc/4.0/
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