[{"volume":10,"author":[{"full_name":"Hernández Rodriguez, Tanja","id":"52466","first_name":"Tanja","last_name":"Hernández Rodriguez"},{"full_name":"Sekulic, Anton","first_name":"Anton","last_name":"Sekulic"},{"full_name":"Lange-Hegermann, Markus","id":"71761","first_name":"Markus","last_name":"Lange-Hegermann"},{"first_name":"Björn","last_name":"Frahm","full_name":"Frahm, Björn","id":"45666"}],"type":"scientific_journal_article","citation":{"chicago-de":"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. <i>Processes</i> 10, Nr. 5. doi:<a href=\"https://doi.org/10.3390/pr10050883\">10.3390/pr10050883</a>, .","chicago":"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.” <i>Processes</i> 10, no. 5 (2022). <a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>.","ufg":"<b>Hernández Rodriguez, Tanja u. a.</b>: Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design, in: <i>Processes</i> 10 (2022), H. 5.","van":"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).","din1505-2-1":"<span style=\"font-variant:small-caps;\">Hernández Rodriguez, Tanja</span> ; <span style=\"font-variant:small-caps;\">Sekulic, Anton</span> ; <span style=\"font-variant:small-caps;\">Lange-Hegermann, Markus</span> ; <span style=\"font-variant:small-caps;\">Frahm, Björn</span>: Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. In: <i>Processes</i> Bd. 10. Basel, MDPI AG (2022), Nr. 5","mla":"Hernández Rodriguez, Tanja, et al. “Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design.” <i>Processes</i>, vol. 10, no. 5, 883, 2022, <a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>.","apa":"Hernández Rodriguez, T., Sekulic, A., Lange-Hegermann, M., &#38; Frahm, B. (2022). Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. <i>Processes</i>, <i>10</i>(5), Article 883. <a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>","ama":"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. <i>Processes</i>. 2022;10(5). doi:<a href=\"https://doi.org/10.3390/pr10050883\">10.3390/pr10050883</a>","short":"T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, B. Frahm, Processes 10 (2022).","ieee":"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,” <i>Processes</i>, vol. 10, no. 5, Art. no. 883, 2022, doi: <a href=\"https://doi.org/10.3390/pr10050883\">10.3390/pr10050883</a>.","bjps":"<b>Hernández Rodriguez T <i>et al.</i></b> (2022) Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design. <i>Processes</i> <b>10</b>.","havard":"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)."},"place":"Basel","user_id":"83781","publication_status":"published","title":"Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design","publication":"Processes","status":"public","publisher":"MDPI AG","publication_identifier":{"eissn":["2227-9717"]},"doi":"10.3390/pr10050883","year":"2022","abstract":[{"lang":"eng","text":"<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."}],"department":[{"_id":"DEP4000"}],"date_updated":"2024-05-21T09:30:15Z","keyword":["Gaussian processes","Bayes optimization","Pareto optimization","multi-objective","cell culture","seed train"],"intvolume":"        10","_id":"11377","issue":"5","article_number":"883","language":[{"iso":"eng"}],"date_created":"2024-04-25T13:35:04Z"},{"keyword":["Gaussian processes","Bayes optimization","Pareto optimization","multi-objective","cell culture","seed train"],"date_updated":"2023-08-16T09:24:16Z","date_created":"2023-08-08T12:58:36Z","_id":"10193","language":[{"iso":"eng"}],"quality_controlled":"1","department":[{"_id":"DEP4000"}],"page":"21-48","series_title":"Processes : open access journal","status":"public","publication":"Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing","doi":"https://doi.org/10.3390/pr10050883","year":"2022","abstract":[{"lang":"eng","text":"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."}],"publication_identifier":{"eisbn":["978-3-0365-5209-5"],"eissn":["2227-9717"],"isbn":["978-3-0365-5210-1"]},"publisher":"MDPI","author":[{"full_name":"Hernández Rodriguez, Tanja","id":"52466","first_name":"Tanja","last_name":"Hernández Rodriguez"},{"full_name":"Sekulic, Anton","first_name":"Anton","last_name":"Sekulic"},{"id":"71761","full_name":"Lange-Hegermann, Markus","first_name":"Markus","last_name":"Lange-Hegermann"},{"first_name":"Björn","last_name":"Frahm","full_name":"Frahm, Björn","id":"45666"}],"type":"book_chapter","place":"Basel","citation":{"ieee":"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 <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, vol. special issue, R. Pörtner and J. Möller, Eds. Basel: MDPI, 2022, pp. 21–48. doi: <a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>.","havard":"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.","bjps":"<b>Hernández Rodriguez T <i>et al.</i></b> (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), <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, vol. special issue. Basel: MDPI, pp. 21–48.","ama":"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. <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>. Vol special issue. Processes : open access journal. MDPI; 2022:21-48. doi:<a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>","apa":"Hernández Rodriguez, T., Sekulic, A., Lange-Hegermann, M., &#38; Frahm, B. (2022). Designing robust biotechnological processes regarding variabilities using multi-objective optimization applied to a biopharmaceutical seed train design. In R. Pörtner &#38; J. Möller (Eds.), <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing: Vol. special issue</i> (pp. 21–48). MDPI. <a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>","short":"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.","din1505-2-1":"<span style=\"font-variant:small-caps;\">Hernández Rodriguez, Tanja</span> ; <span style=\"font-variant:small-caps;\">Sekulic, Anton</span> ; <span style=\"font-variant:small-caps;\">Lange-Hegermann, Markus</span> ; <span style=\"font-variant:small-caps;\">Frahm, Björn</span>: Designing robust biotechnological processes regarding variabilities using multi-objective optimization applied to a biopharmaceutical seed train design. In: <span style=\"font-variant:small-caps;\">Pörtner, R.</span> ; <span style=\"font-variant:small-caps;\">Möller, J.</span> (Hrsg.): <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, <i>Processes : open access journal</i>. Bd. special issue. Basel : MDPI, 2022, S. 21–48","mla":"Hernández Rodriguez, Tanja, et al. “Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design.” <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, edited by Ralf Pörtner and Johannes Möller, vol. special issue, MDPI, 2022, pp. 21–48, <a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>.","chicago":"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 <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, edited by Ralf Pörtner and Johannes Möller, special issue:21–48. Processes : Open Access Journal. Basel: MDPI, 2022. <a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>.","chicago-de":"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: <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, hg. von Ralf Pörtner und Johannes Möller, special issue:21–48. Processes : open access journal. Basel: MDPI. doi:<a href=\"https://doi.org/10.3390/pr10050883\">https://doi.org/10.3390/pr10050883</a>, .","van":"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).","ufg":"<b>Hernández Rodriguez, Tanja u. a.</b>: Designing robust biotechnological processes regarding variabilities using multi-objective optimization applied to a biopharmaceutical seed train design, in: <i>Pörtner, Ralf/Möller, Johannes (Hgg.)</i>: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, Band <i>special issue</i>, Basel 2022 (Processes : open access journal),  S. 21–48."},"volume":"special issue","title":"Designing robust biotechnological processes regarding variabilities using multi-objective optimization applied to a biopharmaceutical seed train design","editor":[{"first_name":"Ralf","last_name":"Pörtner","full_name":"Pörtner, Ralf"},{"full_name":"Möller, Johannes","first_name":"Johannes","last_name":"Möller"}],"publication_status":"published","user_id":"83781"},{"type":"scientific_journal_article","citation":{"chicago":"Hernández Rodriguez, Tanja, Sophie Morerod, Ralf Pörtner, Florian M. Wurm, and Björn Frahm. “Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study.” <i>Processes</i> 9, no. 6 (2021). <a href=\"https://doi.org/10.3390/pr9060964\">https://doi.org/10.3390/pr9060964</a>.","ama":"Hernández Rodriguez T, Morerod S, Pörtner R, Wurm FM, Frahm B. Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. <i>Processes</i>. 2021;9(6). doi:<a href=\"https://doi.org/10.3390/pr9060964\">10.3390/pr9060964</a>","chicago-de":"Hernández Rodriguez, Tanja, Sophie Morerod, Ralf Pörtner, Florian M. Wurm und Björn Frahm. 2021. Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. <i>Processes</i> 9, Nr. 6. doi:<a href=\"https://doi.org/10.3390/pr9060964\">10.3390/pr9060964</a>, .","apa":"Hernández Rodriguez, T., Morerod, S., Pörtner, R., Wurm, F. M., &#38; Frahm, B. (2021). Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. <i>Processes</i>, <i>9</i>(6), Article 964. <a href=\"https://doi.org/10.3390/pr9060964\">https://doi.org/10.3390/pr9060964</a>","short":"T. Hernández Rodriguez, S. Morerod, R. Pörtner, F.M. Wurm, B. Frahm, Processes 9 (2021).","van":"Hernández Rodriguez T, Morerod S, Pörtner R, Wurm FM, Frahm B. Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. Processes. 2021;9(6).","ufg":"<b>Hernández Rodriguez, Tanja u. a.</b>: Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study, in: <i>Processes</i> 9 (2021), H. 6.","ieee":"T. Hernández Rodriguez, S. Morerod, R. Pörtner, F. M. Wurm, and B. Frahm, “Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study,” <i>Processes</i>, vol. 9, no. 6, Art. no. 964, 2021, doi: <a href=\"https://doi.org/10.3390/pr9060964\">10.3390/pr9060964</a>.","havard":"T. Hernández Rodriguez, S. Morerod, R. Pörtner, F.M. Wurm, B. Frahm, Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study, Processes. 9 (2021).","din1505-2-1":"<span style=\"font-variant:small-caps;\">Hernández Rodriguez, Tanja</span> ; <span style=\"font-variant:small-caps;\">Morerod, Sophie</span> ; <span style=\"font-variant:small-caps;\">Pörtner, Ralf</span> ; <span style=\"font-variant:small-caps;\">Wurm, Florian M.</span> ; <span style=\"font-variant:small-caps;\">Frahm, Björn</span>: Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. In: <i>Processes</i> Bd. 9. Basel, MDPI AG (2021), Nr. 6","mla":"Hernández Rodriguez, Tanja, et al. “Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study.” <i>Processes</i>, vol. 9, no. 6, 964, 2021, <a href=\"https://doi.org/10.3390/pr9060964\">https://doi.org/10.3390/pr9060964</a>.","bjps":"<b>Hernández Rodriguez T <i>et al.</i></b> (2021) Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. <i>Processes</i> <b>9</b>."},"place":"Basel","author":[{"first_name":"Tanja","last_name":"Hernández Rodriguez","full_name":"Hernández Rodriguez, Tanja","id":"52466"},{"first_name":"Sophie","last_name":"Morerod","full_name":"Morerod, Sophie"},{"first_name":"Ralf","last_name":"Pörtner","full_name":"Pörtner, Ralf"},{"first_name":"Florian M.","last_name":"Wurm","full_name":"Wurm, Florian M."},{"id":"45666","full_name":"Frahm, Björn","last_name":"Frahm","first_name":"Björn"}],"volume":9,"title":"Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study","user_id":"83781","publication_status":"published","publication":"Processes","status":"public","publisher":"MDPI AG","year":"2021","doi":"10.3390/pr9060964","publication_identifier":{"eissn":["2227-9717"]},"abstract":[{"lang":"eng","text":"<jats:p>concentration is an important objective. The phenotype of the cells in a reactor plays an important role. Are clonal cell populations showing high cell-specific growth rates more favorable than cell lines with higher cell-specific productivities or vice versa? Five clonal Chinese hamster ovary cell populations were analyzed based on the data of a 3-month-stability study. We adapted a mechanistic cell culture model to the experimental data of one such clonally derived cell population. Uncertainties and prior knowledge concerning model parameters were considered using Bayesian parameter estimations. This model was used then to define an inoculum train protocol. Based on this, we subsequently simulated the impacts of differences in growth rates (±10%) and production rates (±10% and ±50%) on the overall cultivation time, including making the inoculum train cultures; the final production phase, the volumetric titer in that bioreactor and the ratio of both, defined as overall process productivity. We showed thus unequivocally that growth rates have a higher impact (up to three times) on overall process productivity and for product output per year, whereas cells with higher productivity can potentially generate higher product concentrations in the production vessel."}],"department":[{"_id":"DEP4000"}],"intvolume":"         9","keyword":["clonal cell population","phenotypic diversity","inoculum train","uncertainty-based","cell culture model","biopharmaceutical manufacturing"],"date_updated":"2024-05-21T09:29:02Z","date_created":"2024-04-25T13:34:26Z","language":[{"iso":"eng"}],"_id":"11376","issue":"6","article_number":"964"}]