Model uncertainty-based evaluation of process strategies during scale-up of biopharmaceutical processes

Reliable scale-up of biopharmaceutical production processes is key in Quality by Design. In this study, a model-based workflow is described to evaluate the bioprocess dynamics during process transfer and scale-up computationally. First, a mathematical model describes the bioprocess dynamics of different state variables (e.g., cell density, titer). Second, the model parameter probability distributions are de- termined at different scales due to measurement uncertainty. Third, the quantified parameter distribu- tions are statistically compared to evaluate if the process dynamics have been changed. This workflow was tested for the scale-up of an antibody-producing CHO fed-batch process. Significant differences were identified between the process development (30 ml) and implementation (250 ml) scale, and the feeding strategy was validated using model-assisted Design of Experiments. Then, the validated process strategy was successfully scaled up to 2 l laboratory and 50 l pilot scale. In summary, the proposed workflow enables a knowledge-driven evaluation tool for bioprocess development.

DDC Class

570: Biowissenschaften, Biologie

Funding(s)

IBÖM04:mDoE-Toolbox2-Neue mDoE Software-Toolbox zur modellgestützten Optimierung biotechnologischer Prozesse

More Funding Information

German Federal Ministry of Education and Research, projects: 031 B0305, 031 B0577A

Lizenz

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

Name

Möller et al. Comp Chem Eng 2020.pdf

Size

3.52 MB

Format

Adobe PDF

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Model uncertainty-based evaluation of process strategies during scale-up of biopharmaceutical processes