Publisher DOI: 10.1007/s00449-019-02089-7
Title: Model-assisted Design of Experiments as a concept for knowledge-based bioprocess development
Language: English
Authors: Möller, Johannes 
Kuchemüller, Kim Beatrice 
Steinmetz, Tobias 
Koopmann, Kirsten 
Pörtner, Ralf  
Keywords: Chinese hamster ovary;Feeding profile;Modeling;Response surface
Issue Date: May-2019
Source: Bioprocess and biosystems engineering 5 (42): 867-882 (2019-05)
Journal or Series Name: Bioprocess and biosystems engineering 
Abstract (english): 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.
URI: http://hdl.handle.net/11420/2682
ISSN: 1615-7591
Institute: Bioprozess- und Biosystemtechnik V-1 
Type: (wissenschaftlicher) Artikel
Funded by: Bundesministerium für Bildung und Forschung 031B0305,031B0577A
Project: IBÖ-04: mDoE-Toolbox - Software zur modellgestützten Optimierung biotechnologischer Prozesse 
IBÖM04:mDoE-Toolbox2-Neue mDoE Software-Toolbox zur modellgestützten Optimierung biotechnologischer Prozesse 
Modellgestützte Bioprozessentwicklung zur Herstellung von natürlichen Milcholigosacchariden für medizinische Anwendungen 
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