LAPSE:2019.0665
Published Article
LAPSE:2019.0665
Accelerating Biologics Manufacturing by Upstream Process Modelling
Martin Kornecki, Jochen Strube
July 25, 2019
Intensified and accelerated development processes are being demanded by the market, as innovative biopharmaceuticals such as virus-like particles, exosomes, cell and gene therapy, as well as recombinant proteins and peptides will possess no available platform approach. Therefore, methods that are able to accelerate this development are preferred. Especially, physicochemical rigorous process models, based on all relevant effects of fluid dynamics, phase equilibrium, and mass transfer, can be predictive, if the model is verified and distinctly quantitatively validated. In this approach, a macroscopic kinetic model based on Monod kinetics for mammalian cell cultivation is developed and verified according to a general valid model validation workflow. The macroscopic model is verified and validated on the basis of four decision criteria (plausibility, sensitivity, accuracy and precision as well as equality). The process model workflow is subjected to a case study, comprising a Chinese hamster ovary fed-batch cultivation for the production of a monoclonal antibody. By performing the workflow, it was found that, based on design of experiments and Monte Carlo simulation, the maximum growth rate µmax exhibited the greatest influence on model variables such as viable cell concentration XV and product concentration. In addition, partial least squares regressions statistically evaluate the correlations between a higher µmax and a higher cell and product concentration, as well as a higher substrate consumption.
Keywords
biologics, manufacturing, Modelling, Monod kinetics, Process Intensification, upstream processing
Subject
Suggested Citation
Kornecki M, Strube J. Accelerating Biologics Manufacturing by Upstream Process Modelling. (2019). LAPSE:2019.0665
Author Affiliations
Kornecki M: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
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Journal Name
Processes
Volume
7
Issue
3
Article Number
E166
Year
2019
Publication Date
2019-03-21
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr7030166, Publication Type: Journal Article
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LAPSE:2019.0665
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doi:10.3390/pr7030166
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Jul 25, 2019
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CC BY 4.0
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Jul 25, 2019
 
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Jul 25, 2019
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Original Submitter
Calvin Tsay
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