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, in: R. Pörtner, J. Möller (Eds.), Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, MDPI, Basel, 2022, pp. 21–48.

Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Sammelwerk - Beitrag | Veröffentlicht | Englisch
Herausgeber*in
;
Abstract
Development and optimization of biopharmaceutical production processes with cell cultures is cost- and time-consuming and often performed rather empirically. Efficient optimization of multiple objectives such as process time, viable cell density, number of operating steps & 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 (<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
Buchtitel
Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing
Band
special issue
Seite
21-48
eISSN
ELSA-ID

Zitieren

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. In: Pörtner R, Möller J, eds. Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing. Vol special issue. Processes : open access journal. MDPI; 2022:21-48. doi:https://doi.org/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. In R. Pörtner & J. Möller (Eds.), Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing: Vol. special issue (pp. 21–48). MDPI. 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. In Pörtner R and Möller J (eds), Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, vol. special issue. Basel: MDPI, pp. 21–48.
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.” In Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, edited by Ralf Pörtner and Johannes Möller, special issue:21–48. Processes : Open Access Journal. Basel: MDPI, 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. In: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, hg. von Ralf Pörtner und Johannes Möller, special issue:21–48. Processes : open access journal. Basel: MDPI. doi:https://doi.org/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: Pörtner, R. ; Möller, J. (Hrsg.): Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, Processes : open access journal. Bd. special issue. Basel : MDPI, 2022, S. 21–48
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, in: R. Pörtner, J. Möller (Eds.), Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, MDPI, Basel, 2022: pp. 21–48.
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,” in Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, vol. special issue, R. Pörtner and J. Möller, Eds. Basel: MDPI, 2022, pp. 21–48. doi: https://doi.org/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.” Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, edited by Ralf Pörtner and Johannes Möller, vol. special issue, MDPI, 2022, pp. 21–48, 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: Pörtner, Ralf/Möller, Johannes (Hgg.): Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, Band special issue, Basel 2022 (Processes : open access journal),  S. 21–48.
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. In: Pörtner R, Möller J, editors. Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing. Basel: MDPI; 2022. p. 21–48. (Processes : open access journal; vol. special issue).

Export

Markierte Publikationen

Open Data ELSA

Suchen in

Google Scholar
ISBN Suche