Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design

T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, B. Frahm, Processes 10 (2022).

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Zeitschriftenaufsatz (wiss.) | Veröffentlicht | Englisch
Abstract
<jats:p>consuming and often performed rather empirically. Efficient optimization of multiple objectives such as process time, viable cell density, number of operating steps &amp; cultivation scales, required medium, amount of product as well as product quality depicts a promising approach. This contribution presents a workflow which couples uncertainty-based upstream simulation and Bayes optimization using Gaussian processes. Its application is demonstrated in a simulation case study for a relevant industrial task in process development, the design of a robust cell culture expansion process (seed train), meaning that despite uncertainties and variabilities concerning cell growth, low variations of viable cell density during the seed train are obtained. Compared to a non-optimized reference seed train, the optimized process showed much lower deviation rates regarding viable cell densities (&lt;10% instead of 41.7%) using five or four shake flask scales and seed train duration could be reduced by 56 h from 576 h to 520 h. Overall, it is shown that applying Bayes optimization allows for optimization of a multi-objective optimization function with several optimizable input variables and under a considerable amount of constraints with a low computational effort. This approach provides the potential to be used in the form of a decision tool, e.g., for the choice of an optimal and robust seed train design or for further optimization tasks within process development.
Erscheinungsjahr
Zeitschriftentitel
Processes
Band
10
Zeitschriftennummer
5
Artikelnummer
883
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Hernández Rodriguez T, Sekulic A, Lange-Hegermann M, Frahm B. Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. Processes. 2022;10(5). doi:10.3390/pr10050883
Hernández Rodriguez, T., Sekulic, A., Lange-Hegermann, M., & Frahm, B. (2022). Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. Processes, 10(5), Article 883. https://doi.org/10.3390/pr10050883
Hernández Rodriguez T et al. (2022) Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. Processes 10.
Hernández Rodriguez, Tanja, Anton Sekulic, Markus Lange-Hegermann, and Björn Frahm. “Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design.” Processes 10, no. 5 (2022). https://doi.org/10.3390/pr10050883.
Hernández Rodriguez, Tanja, Anton Sekulic, Markus Lange-Hegermann und Björn Frahm. 2022. Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. Processes 10, Nr. 5. doi:10.3390/pr10050883, .
Hernández Rodriguez, Tanja ; Sekulic, Anton ; Lange-Hegermann, Markus ; Frahm, Björn: Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. In: Processes Bd. 10. Basel, MDPI AG (2022), Nr. 5
T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, B. Frahm, Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design, Processes. 10 (2022).
T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, and B. Frahm, “Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design,” Processes, vol. 10, no. 5, Art. no. 883, 2022, doi: 10.3390/pr10050883.
Hernández Rodriguez, Tanja, et al. “Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design.” Processes, vol. 10, no. 5, 883, 2022, https://doi.org/10.3390/pr10050883.
Hernández Rodriguez, Tanja u. a.: Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design, in: Processes 10 (2022), H. 5.
Hernández Rodriguez T, Sekulic A, Lange-Hegermann M, Frahm B. Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. Processes. 2022;10(5).

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