--- _id: '11376' abstract: - lang: eng text: 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. article_number: '964' author: - first_name: Tanja full_name: Hernández Rodriguez, Tanja id: '52466' last_name: Hernández Rodriguez - first_name: Sophie full_name: Morerod, Sophie last_name: Morerod - first_name: Ralf full_name: Pörtner, Ralf last_name: Pörtner - first_name: Florian M. full_name: Wurm, Florian M. last_name: Wurm - first_name: Björn full_name: Frahm, Björn id: '45666' last_name: Frahm citation: 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. Processes. 2021;9(6). doi:10.3390/pr9060964 apa: Hernández Rodriguez, T., Morerod, S., Pörtner, R., Wurm, F. M., & Frahm, B. (2021). Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. Processes, 9(6), Article 964. https://doi.org/10.3390/pr9060964 bjps: Hernández Rodriguez T et al. (2021) Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. Processes 9. 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.” Processes 9, no. 6 (2021). https://doi.org/10.3390/pr9060964. 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. Processes 9, Nr. 6. doi:10.3390/pr9060964, . din1505-2-1: 'Hernández Rodriguez, Tanja ; Morerod, Sophie ; Pörtner, Ralf ; Wurm, Florian M. ; Frahm, Björn: Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study. In: Processes Bd. 9. Basel, MDPI AG (2021), Nr. 6' 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). 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,” Processes, vol. 9, no. 6, Art. no. 964, 2021, doi: 10.3390/pr9060964.' mla: Hernández Rodriguez, Tanja, et al. “Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study.” Processes, vol. 9, no. 6, 964, 2021, https://doi.org/10.3390/pr9060964. short: T. Hernández Rodriguez, S. Morerod, R. Pörtner, F.M. Wurm, B. Frahm, Processes 9 (2021). ufg: 'Hernández Rodriguez, Tanja u. a.: Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study, in: Processes 9 (2021), H. 6.' 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). date_created: 2024-04-25T13:34:26Z date_updated: 2024-05-21T09:29:02Z department: - _id: DEP4000 doi: 10.3390/pr9060964 intvolume: ' 9' issue: '6' keyword: - clonal cell population - phenotypic diversity - inoculum train - uncertainty-based - cell culture model - biopharmaceutical manufacturing language: - iso: eng place: Basel publication: Processes publication_identifier: eissn: - 2227-9717 publication_status: published publisher: MDPI AG status: public title: Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study type: scientific_journal_article user_id: '83781' volume: 9 year: '2021' ... --- _id: '7983' abstract: - lang: eng text: For the manufacturing of complex biopharmaceuticals using bioreactors with cultivated mammalian cells, high product 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. author: - first_name: Tanja full_name: Hernández Rodriguez, Tanja id: '52466' last_name: Hernández Rodriguez - first_name: Sophie full_name: Morerod, Sophie last_name: Morerod - first_name: Ralf full_name: Pörtner, Ralf last_name: Pörtner - first_name: Florian M. full_name: Wurm, Florian M. last_name: Wurm - first_name: Björn full_name: Frahm, Björn id: '45666' last_name: Frahm citation: 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. In: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing. Vol special issue. Processes : open access journal . MDPI; 2021:49-74. doi:10.3390/pr9060964' apa: 'Hernández Rodriguez, T., Morerod, S., Pörtner, R., Wurm, F. M., & Frahm, B. (2021). Considerations of the impacts of cell-specific growth and production rate on clone selection – a simulation study. In Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing: Vol. special issue (pp. 49–74). MDPI. https://doi.org/10.3390/pr9060964' bjps: 'Hernández Rodriguez T et al. (2021) Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection – a Simulation Study. Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, vol. special issue. Basel: MDPI, pp. 49–74.' 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.” In Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, special issue:49–74. Processes : Open Access Journal . Basel: MDPI, 2021. https://doi.org/10.3390/pr9060964.' 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. In: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, special issue:49–74. Processes : open access journal . Basel: MDPI. doi:10.3390/pr9060964, .' din1505-2-1: 'Hernández Rodriguez, Tanja ; Morerod, Sophie ; Pörtner, Ralf ; Wurm, Florian M. ; Frahm, Björn: Considerations of the impacts of cell-specific growth and production rate on clone selection – a simulation study. In: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, Processes : open access journal . Bd. special issue. Basel : MDPI, 2021, S. 49–74' 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, in: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, MDPI, Basel, 2021: pp. 49–74.' 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,” in Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, vol. special issue, Basel: MDPI, 2021, pp. 49–74. doi: 10.3390/pr9060964.' mla: Hernández Rodriguez, Tanja, et al. “Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection – a Simulation Study.” Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, vol. special issue, MDPI, 2021, pp. 49–74, https://doi.org/10.3390/pr9060964. short: 'T. Hernández Rodriguez, S. Morerod, R. Pörtner, F.M. Wurm, B. Frahm, in: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, MDPI, Basel, 2021, pp. 49–74.' ufg: 'Hernández Rodriguez, Tanja u. a.: Considerations of the impacts of cell-specific growth and production rate on clone selection – a simulation study, in: o. Hg.: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, Band special issue, Basel 2021 (Processes : open access journal ),  S. 49–74.' 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. In: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing. Basel: MDPI; 2021. p. 49–74. (Processes : open access journal ; vol. special issue).' date_created: 2022-05-05T12:55:52Z date_updated: 2023-08-16T09:17:50Z department: - _id: DEP4021 doi: 10.3390/pr9060964 keyword: - clonal cell population - phenotypic diversity - inoculum train - uncertainty-based - cell culture model - biopharmaceutical manufacturing language: - iso: eng page: 49-74 place: Basel publication: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing publication_identifier: eisbn: - 978-3-0365-5209-5 isbn: - 978-3-0365-5210-1 issn: - '2227-9717 ' publication_status: published publisher: MDPI quality_controlled: '1' series_title: 'Processes : open access journal ' status: public title: Considerations of the impacts of cell-specific growth and production rate on clone selection – a simulation study type: book_chapter user_id: '83781' volume: special issue year: '2021' ...