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Design of cell expansion processes for adherent-growing cells with mDoE-workflow
Citation Link: https://doi.org/10.15480/882.5176
Publikationstyp
Journal Article
Date Issued
2023-04-25
Sprache
English
Author(s)
Institut
TORE-DOI
Journal
Volume
23
Issue
5
Article Number
e2200059
Citation
Engineering in Life Sciences 23 (5): e2200059 (2023)
Publisher DOI
Scopus ID
Publisher
Wiley-VCH
Adherent cells, mammalian or human, are ubiquitous for production of viral vaccines, in gene therapy and in immuno-oncology. The development of a cell-expansion process with adherent cells is challenging as scale-up requires the expansion of the cell culture surface. Microcarrier (MC)-based cultures are still predominate. However, the development of MC processes from scratch possesses particular challenges due to their complexity. A novel approach for the reduction of development times and costs of cell propagation processes is the combination of mathematical process models with statistical optimization methods, called model-assisted Design of Experiments (mDoE). In this study, an mDoE workflow was evaluated successfully for the design of a MC-based expansion process of adherent L929 cells at a very early stage of development with limited prior knowledge. At the start, the analytical methods and the screening of appropriate MCs were evaluated. Then, cause-effect relationships (e.g., cell growth related to medium conditions) were worked out, and a mathematical process model was set-up and adapted to experimental data for modeling purposes. The model was subsequently used in mDoE to identify optimized process conditions, which were proven experimentally. An eight-fold increase in cell yield was achieved basically by reducing the initial MC concentration.
Subjects
early stage development
L929
mathematical process model
microcarrier culture
model-assisted Design of Experiments (mDoE)
DDC Class
004: Informatik
510: Mathematik
600: Technik
620: Ingenieurwissenschaften
Publication version
acceptedVersion
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