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  4. Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection-A Simulation Study
 
research article

Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection-A Simulation Study

Hernandez Rodriguez, Tanja
•
Morerod, Sophie
•
Poertner, Ralf
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June 1, 2021
Processes

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.

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Type
research article
DOI
10.3390/pr9060964
Web of Science ID

WOS:000667393400001

Author(s)
Hernandez Rodriguez, Tanja
Morerod, Sophie
Poertner, Ralf
Wurm, Florian M.  
Frahm, Bjorn
Date Issued

2021-06-01

Published in
Processes
Volume

9

Issue

6

Start page

964

Subjects

Engineering, Chemical

•

Engineering

•

clonal cell population

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phenotypic diversity

•

inoculum train

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uncertainty-based

•

cell culture model

•

biopharmaceutical manufacturing

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LBTC  
Available on Infoscience
July 17, 2021
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/180009
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