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Publisher DOI: 10.3390/pr9060964
Title: Considerations of the impacts of cell-specific growth and production rate on clone selection : a simulation study
Language: English
Authors: Hernández Rodríguez, Tanja 
Morerod, Sophie 
Pörtner, Ralf  
Wurm, Florian M. 
Frahm, Björn 
Keywords: clonal cell population;phenotypic diversity;inoculum train;uncertainty-based;cell culture model;biopharmaceutical manufacturing
Issue Date: 28-May-2021
Publisher: Multidisciplinary Digital Publishing Institute
Source: Processes 9 (6): 964 (2021)
Journal: Processes 
Abstract (english): 
For the manufacturing of complex biopharmaceuticals using bioreactors with cultivated mammalian cells, high product concentration is an important objective. The phenotype of the cells in a reactor plays an important role. Are clonal cell populations showing high cell-specific growth rates more favorable than cell lines with higher cell-specific productivities or vice versa? Five clonal Chinese hamster ovary cell populations were analyzed based on the data of a 3-month-stability study. We adapted a mechanistic cell culture model to the experimental data of one such clonally derived cell population. Uncertainties and prior knowledge concerning model parameters were considered using Bayesian parameter estimations. This model was used then to define an inoculum train protocol. Based on this, we subsequently simulated the impacts of differences in growth rates (±10%) and production rates (±10% and ±50%) on the overall cultivation time, including making the inoculum train cultures; the final production phase, the volumetric titer in that bioreactor and the ratio of both, defined as overall process productivity. We showed thus unequivocally that growth rates have a higher impact (up to three times) on overall process productivity and for product output per year, whereas cells with higher productivity can potentially generate higher product concentrations in the production vessel.
DOI: 10.15480/882.3596
ISSN: 2227-9717
Other Identifiers: doi: 10.3390/pr9060964
Institute: Bioprozess- und Biosystemtechnik V-1 
Document Type: Article
License: CC BY 4.0 (Attribution) CC BY 4.0 (Attribution)
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