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- Title
Model-assisted Design of Experiments as a concept for knowledge-based bioprocess development.
- Authors
Möller, Johannes; Kuchemüller, Kim B.; Steinmetz, Tobias; Koopmann, Kirsten S.; Pörtner, Ralf
- Abstract
Design of Experiments methods offer systematic tools for bioprocess development in Quality by Design, but their major drawback is the user-defined choice of factor boundary values. This can lead to several iterative rounds of time-consuming and costly experiments. In this study, a model-assisted Design of Experiments concept is introduced for the knowledge-based reduction of boundary values. First, the parameters of a mathematical process model are estimated. Second, the investigated factor combinations are simulated instead of experimentally derived and a constraint-based evaluation and optimization of the experimental space can be performed. The concept is discussed for the optimization of an antibody-producing Chinese hamster ovary batch and bolus fed-batch process. The same optimal process strategies were found if comparing the model-assisted Design of Experiments (4 experiments each) and traditional Design of Experiments (16 experiments for batch and 29 experiments for fed-batch). This approach significantly reduces the number of experiments needed for knowledge-based bioprocess development.
- Subjects
EXPERIMENTAL design; CONCEPTS; OVARIES; HAMSTERS; MATHEMATICAL models
- Publication
Bioprocess & Biosystems Engineering, 2019, Vol 42, Issue 5, p867
- ISSN
1615-7591
- Publication type
Article
- DOI
10.1007/s00449-019-02089-7