Design of cell expansion processes for adherent-growing cells with mDoE-workflow

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

Funding(s)

Open-Access-Publikationskosten / 2022-2024 / Technische Universität Hamburg (TUHH)

Publication version

acceptedVersion

Lizenz

https://creativecommons.org/licenses/by/4.0/

Name

Engineering in Life Sciences - 2023 - Kuchem ller - Design of cell expansion processes for adherent‐growing cells with.pdf

Size

1.85 MB

Format

Adobe PDF

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Design of cell expansion processes for adherent-growing cells with mDoE-workflow