Kuchemüller, Kim B.Kim B.KuchemüllerPörtner, RalfRalfPörtnerMöller, JohannesJohannesMöller2023-06-152023-06-152023-04-25Engineering in Life Sciences 23 (5): e2200059 (2023)http://hdl.handle.net/11420/15397Adherent 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.en1618-286320235Wiley-VCHhttps://creativecommons.org/licenses/by/4.0/early stage developmentL929mathematical process modelmicrocarrier culturemodel-assisted Design of Experiments (mDoE)InformatikMathematikTechnikIngenieurwissenschaftenJournal Article10.15480/882.517610.1002/elsc.20220005910.15480/882.5176Other