[{"abstract":[{"text":"In anaerobic technology, pH values are crucial for targeted volatile fatty acid production. While pH dynamics can be modeled using the Anaerobic Digestion Model No. 1 (ADM1), simulation results may be biased. To address this issue, the pH prediction routine of Visual Water, a specialized water chemistry simulator, was validated. Unlike ADM1, it accounts for ionic strength and activities while also providing an automated uncertainty analysis. The analysis revealed Visual Water simulations to better fit measured pH data from acidic solutions in a miniaturized stirred-tank reactor.","lang":"eng"}],"page":"528-534","keyword":["Anaerobic Digestion Model No. 1 (ADM1)","Anaerobic technology","pH simulation","Uncertainty assessment","Visual Water"],"status":"public","user_id":"83781","year":"2024","department":[{"_id":"DEP4000"}],"date_updated":"2025-06-25T12:42:09Z","doi":"10.1002/cite.202300188","external_id":{"isi":["001169606600001"]},"quality_controlled":"1","issue":"4","publisher":"Wiley","type":"scientific_journal_article","_id":"12402","publication":"Chemie Ingenieur Technik","title":"Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator","place":"Weinheim","citation":{"havard":"P. Kosse, T. Hernández Rodriguez, B. Frahm, M. Lübken, M. Wichern, Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator, Chemie Ingenieur Technik. 96 (2024) 528–534.","chicago-de":"Kosse, Pascal, Tanja Hernández Rodriguez, Björn Frahm, Manfred Lübken und Marc Wichern. 2024. Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator. <i>Chemie Ingenieur Technik</i> 96, Nr. 4: 528–534. doi:<a href=\"https://doi.org/10.1002/cite.202300188\">10.1002/cite.202300188</a>, .","ufg":"<b>Kosse, Pascal u. a.</b>: Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator, in: <i>Chemie Ingenieur Technik</i> 96 (2024), H. 4,  S. 528–534.","mla":"Kosse, Pascal, et al. “Comparative Analysis of PH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator.” <i>Chemie Ingenieur Technik</i>, vol. 96, no. 4, 2024, pp. 528–34, <a href=\"https://doi.org/10.1002/cite.202300188\">https://doi.org/10.1002/cite.202300188</a>.","apa":"Kosse, P., Hernández Rodriguez, T., Frahm, B., Lübken, M., &#38; Wichern, M. (2024). Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator. <i>Chemie Ingenieur Technik</i>, <i>96</i>(4), 528–534. <a href=\"https://doi.org/10.1002/cite.202300188\">https://doi.org/10.1002/cite.202300188</a>","short":"P. Kosse, T. Hernández Rodriguez, B. Frahm, M. Lübken, M. Wichern, Chemie Ingenieur Technik 96 (2024) 528–534.","van":"Kosse P, Hernández Rodriguez T, Frahm B, Lübken M, Wichern M. Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator. Chemie Ingenieur Technik. 2024;96(4):528–34.","ama":"Kosse P, Hernández Rodriguez T, Frahm B, Lübken M, Wichern M. Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator. <i>Chemie Ingenieur Technik</i>. 2024;96(4):528-534. doi:<a href=\"https://doi.org/10.1002/cite.202300188\">10.1002/cite.202300188</a>","ieee":"P. Kosse, T. Hernández Rodriguez, B. Frahm, M. Lübken, and M. Wichern, “Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator,” <i>Chemie Ingenieur Technik</i>, vol. 96, no. 4, pp. 528–534, 2024, doi: <a href=\"https://doi.org/10.1002/cite.202300188\">10.1002/cite.202300188</a>.","chicago":"Kosse, Pascal, Tanja Hernández Rodriguez, Björn Frahm, Manfred Lübken, and Marc Wichern. “Comparative Analysis of PH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator.” <i>Chemie Ingenieur Technik</i> 96, no. 4 (2024): 528–34. <a href=\"https://doi.org/10.1002/cite.202300188\">https://doi.org/10.1002/cite.202300188</a>.","din1505-2-1":"<span style=\"font-variant:small-caps;\">Kosse, Pascal</span> ; <span style=\"font-variant:small-caps;\">Hernández Rodriguez, Tanja</span> ; <span style=\"font-variant:small-caps;\">Frahm, Björn</span> ; <span style=\"font-variant:small-caps;\">Lübken, Manfred</span> ; <span style=\"font-variant:small-caps;\">Wichern, Marc</span>: Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator. In: <i>Chemie Ingenieur Technik</i> Bd. 96. Weinheim, Wiley (2024), Nr. 4, S. 528–534","bjps":"<b>Kosse P <i>et al.</i></b> (2024) Comparative Analysis of PH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator. <i>Chemie Ingenieur Technik</i> <b>96</b>, 528–534."},"date_created":"2025-01-29T13:49:16Z","language":[{"iso":"eng"}],"volume":96,"publication_status":"published","isi":"1","intvolume":"        96","author":[{"full_name":"Kosse, Pascal","last_name":"Kosse","first_name":"Pascal"},{"first_name":"Tanja","full_name":"Hernández Rodriguez, Tanja","last_name":"Hernández Rodriguez","id":"52466"},{"first_name":"Björn","id":"45666","last_name":"Frahm","full_name":"Frahm, Björn"},{"first_name":"Manfred","full_name":"Lübken, Manfred","last_name":"Lübken"},{"first_name":"Marc","full_name":"Wichern, Marc","last_name":"Wichern"}],"publication_identifier":{"eissn":["1522-2640"],"issn":["0009-286X"]}},{"issue":"12","external_id":{"isi":["001073579300001"]},"quality_controlled":"1","date_updated":"2025-06-26T07:50:29Z","doi":"10.1002/cite.202300082","type":"scientific_journal_article","publisher":"Wiley","keyword":["Acid-base equilibria","Carboxylic acids","Dissociation constants","pH calculation software","Uncertainty assessment"],"page":"1960-1969","abstract":[{"text":"Accurate pH calculations are essential for scientists across different disciplines to design optimal reactor solutions, but they can be arduous to calculate for complex acid-base solutions. Visual Water is a powerful software tool that provides accurate pH calculations with automated mathematical uncertainty analysis. Its workflow is presented and validated using acids and bases, showing a deviation of < 0.2 pH units between measured and calculated pH values. This highlights the software's reliability, which can help to simplify the work of non-experts in water chemistry.","lang":"eng"}],"department":[{"_id":"DEP4000"}],"user_id":"83781","year":"2023","status":"public","title":"Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations","publication_identifier":{"issn":["0009-286X"],"eissn":["1522-2640"]},"intvolume":"        95","author":[{"first_name":"Pascal","full_name":"Kosse, Pascal","last_name":"Kosse"},{"first_name":"Tanja","last_name":"Hernández Rodriguez","id":"52466","full_name":"Hernández Rodriguez, Tanja"},{"first_name":"Björn","id":"45666","last_name":"Frahm","full_name":"Frahm, Björn"},{"last_name":"Lübken","full_name":"Lübken, Manfred","first_name":"Manfred"},{"full_name":"Wichern, Marc","last_name":"Wichern","first_name":"Marc"}],"isi":"1","volume":95,"publication_status":"published","language":[{"iso":"eng"}],"date_created":"2024-04-26T06:52:48Z","citation":{"havard":"P. Kosse, T. Hernández Rodriguez, B. Frahm, M. Lübken, M. Wichern, Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations, Chemie Ingenieur Technik. 95 (2023) 1960–1969.","ufg":"<b>Kosse, Pascal u. a.</b>: Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations, in: <i>Chemie Ingenieur Technik</i> 95 (2023), H. 12,  S. 1960–1969.","chicago-de":"Kosse, Pascal, Tanja Hernández Rodriguez, Björn Frahm, Manfred Lübken und Marc Wichern. 2023. Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations. <i>Chemie Ingenieur Technik</i> 95, Nr. 12: 1960–1969. doi:<a href=\"https://doi.org/10.1002/cite.202300082\">10.1002/cite.202300082</a>, .","short":"P. Kosse, T. Hernández Rodriguez, B. Frahm, M. Lübken, M. Wichern, Chemie Ingenieur Technik 95 (2023) 1960–1969.","apa":"Kosse, P., Hernández Rodriguez, T., Frahm, B., Lübken, M., &#38; Wichern, M. (2023). Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations. <i>Chemie Ingenieur Technik</i>, <i>95</i>(12), 1960–1969. <a href=\"https://doi.org/10.1002/cite.202300082\">https://doi.org/10.1002/cite.202300082</a>","mla":"Kosse, Pascal, et al. “Validation and Uncertainty Assessment of a Software‐Integrated Workflow for PH Calculations.” <i>Chemie Ingenieur Technik</i>, vol. 95, no. 12, 2023, pp. 1960–69, <a href=\"https://doi.org/10.1002/cite.202300082\">https://doi.org/10.1002/cite.202300082</a>.","ama":"Kosse P, Hernández Rodriguez T, Frahm B, Lübken M, Wichern M. Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations. <i>Chemie Ingenieur Technik</i>. 2023;95(12):1960-1969. doi:<a href=\"https://doi.org/10.1002/cite.202300082\">10.1002/cite.202300082</a>","van":"Kosse P, Hernández Rodriguez T, Frahm B, Lübken M, Wichern M. Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations. Chemie Ingenieur Technik. 2023;95(12):1960–9.","ieee":"P. Kosse, T. Hernández Rodriguez, B. Frahm, M. Lübken, and M. Wichern, “Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations,” <i>Chemie Ingenieur Technik</i>, vol. 95, no. 12, pp. 1960–1969, 2023, doi: <a href=\"https://doi.org/10.1002/cite.202300082\">10.1002/cite.202300082</a>.","chicago":"Kosse, Pascal, Tanja Hernández Rodriguez, Björn Frahm, Manfred Lübken, and Marc Wichern. “Validation and Uncertainty Assessment of a Software‐Integrated Workflow for PH Calculations.” <i>Chemie Ingenieur Technik</i> 95, no. 12 (2023): 1960–69. <a href=\"https://doi.org/10.1002/cite.202300082\">https://doi.org/10.1002/cite.202300082</a>.","bjps":"<b>Kosse P <i>et al.</i></b> (2023) Validation and Uncertainty Assessment of a Software‐Integrated Workflow for PH Calculations. <i>Chemie Ingenieur Technik</i> <b>95</b>, 1960–1969.","din1505-2-1":"<span style=\"font-variant:small-caps;\">Kosse, Pascal</span> ; <span style=\"font-variant:small-caps;\">Hernández Rodriguez, Tanja</span> ; <span style=\"font-variant:small-caps;\">Frahm, Björn</span> ; <span style=\"font-variant:small-caps;\">Lübken, Manfred</span> ; <span style=\"font-variant:small-caps;\">Wichern, Marc</span>: Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations. In: <i>Chemie Ingenieur Technik</i> Bd. 95. Weinheim, Wiley (2023), Nr. 12, S. 1960–1969"},"place":"Weinheim","_id":"11385","publication":"Chemie Ingenieur Technik"},{"doi":"https://doi.org/10.1017/pds.2023.266 ","date_updated":"2023-06-29T12:49:02Z","quality_controlled":"1","type":"conference_editor_article","publisher":"Cambridge University Press","keyword":["Product Lifecycle Management (PLM)","Change Impact","Complexity","Uncertainty"],"abstract":[{"lang":"eng","text":"During product development, the customer or internal stakeholders initiate changes concerning the components or functions of a cyber-physical system (CPS). The complexity of such a CPS causes difficulties in evaluating the effects of a component change. Accordingly, product developers need an assistance system to quantify the impact of a component change on hardware, software, system functions, and production processes. Therefore, this paper focuses on concepts to evaluate the effects of component, functional, and process changes and contributes to its clarification and further understanding of the importance and requirements for such an assistance system. The literature review assesses the identified methods regarding their objectives, application objects, level of automation, and relations characteristics. However, the literature review pointed out that the change prediction method from Clarkson et al. (2004) is well-established in the literature and able to quantify the impact of a change."}],"page":"2655-2664","conference":{"location":"Bordeaux, Frankreich","start_date":"2023-07-24","end_date":"2023-07-28","name":"24th International Conference on Engineering Design (ICED 2023)"},"user_id":"15514","year":"2023","status":"public","main_file_link":[{"open_access":"1","url":"https://www.cambridge.org/core/journals/proceedings-of-the-design-society/article/methods-of-change-impact-analysis-for-product-development-a-systematic-review-of-the-literature/F33BF904B25755EF60388FB7A6A3BAAF"}],"title":"METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE","author":[{"first_name":"Viktoria","last_name":"Mordaschew","id":"79005","full_name":"Mordaschew, Viktoria"},{"first_name":"Jan-Phillip","id":"75846","last_name":"Herrmann","full_name":"Herrmann, Jan-Phillip"},{"first_name":"Sven","last_name":"Tackenberg","id":"71470","full_name":"Tackenberg, Sven"}],"publication_identifier":{"eissn":["2732-527X "]},"citation":{"chicago-de":"Mordaschew, Viktoria, Jan-Phillip Herrmann und Sven Tackenberg. 2023. <i>METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE</i>. <i>Proceedings of the International Conference onEngineering Design (ICED23)</i>. Cambridge: Cambridge University Press. doi:<a href=\"https://doi.org/10.1017/pds.2023.266 \">https://doi.org/10.1017/pds.2023.266 </a>, .","ufg":"<b>Mordaschew, Viktoria/Herrmann, Jan-Phillip/Tackenberg, Sven</b>: METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE, Cambridge 2023.","mla":"Mordaschew, Viktoria, et al. “METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE.” <i>Proceedings of the International Conference OnEngineering Design (ICED23)</i>, Cambridge University Press, 2023, pp. 2655–64, <a href=\"https://doi.org/10.1017/pds.2023.266 \">https://doi.org/10.1017/pds.2023.266 </a>.","apa":"Mordaschew, V., Herrmann, J.-P., &#38; Tackenberg, S. (2023). METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE. In <i>Proceedings of the International Conference onEngineering Design (ICED23)</i> (pp. 2655–2664). Cambridge University Press. <a href=\"https://doi.org/10.1017/pds.2023.266 \">https://doi.org/10.1017/pds.2023.266 </a>","short":"V. Mordaschew, J.-P. Herrmann, S. Tackenberg, METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE, Cambridge University Press, Cambridge, 2023.","havard":"V. Mordaschew, J.-P. Herrmann, S. Tackenberg, METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE, Cambridge University Press, Cambridge, 2023.","chicago":"Mordaschew, Viktoria, Jan-Phillip Herrmann, and Sven Tackenberg. <i>METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE</i>. <i>Proceedings of the International Conference OnEngineering Design (ICED23)</i>. Cambridge: Cambridge University Press, 2023. <a href=\"https://doi.org/10.1017/pds.2023.266 \">https://doi.org/10.1017/pds.2023.266 </a>.","din1505-2-1":"<span style=\"font-variant:small-caps;\">Mordaschew, Viktoria</span> ; <span style=\"font-variant:small-caps;\">Herrmann, Jan-Phillip</span> ; <span style=\"font-variant:small-caps;\">Tackenberg, Sven</span>: <i>METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE</i>. Cambridge : Cambridge University Press, 2023","bjps":"<b>Mordaschew V, Herrmann J-P and Tackenberg S</b> (2023) <i>METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE</i>. Cambridge: Cambridge University Press.","van":"Mordaschew V, Herrmann JP, Tackenberg S. METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE. Proceedings of the International Conference onEngineering Design (ICED23). Cambridge: Cambridge University Press; 2023.","ama":"Mordaschew V, Herrmann JP, Tackenberg S. <i>METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE</i>. Cambridge University Press; 2023:2655-2664. doi:<a href=\"https://doi.org/10.1017/pds.2023.266 \">https://doi.org/10.1017/pds.2023.266 </a>","ieee":"V. Mordaschew, J.-P. Herrmann, and S. Tackenberg, <i>METHODS OF CHANGE IMPACT ANALYSIS FOR PRODUCT DEVELOPMENT: A SYSTEMATIC REVIEW OF THE LITERATURE</i>. Cambridge: Cambridge University Press, 2023, pp. 2655–2664. doi: <a href=\"https://doi.org/10.1017/pds.2023.266 \">https://doi.org/10.1017/pds.2023.266 </a>."},"place":"Cambridge","publication_status":"published","language":[{"iso":"eng"}],"date_created":"2023-06-26T10:58:11Z","oa":"1","_id":"10010","publication":"Proceedings of the International Conference onEngineering Design (ICED23)"},{"publication_identifier":{"eissn":["2227-9717"]},"intvolume":"         9","author":[{"first_name":"Tanja","id":"52466","last_name":"Hernández Rodriguez","full_name":"Hernández Rodriguez, Tanja"},{"full_name":"Morerod, Sophie","last_name":"Morerod","first_name":"Sophie"},{"full_name":"Pörtner, Ralf","last_name":"Pörtner","first_name":"Ralf"},{"full_name":"Wurm, Florian M.","last_name":"Wurm","first_name":"Florian M."},{"full_name":"Frahm, Björn","id":"45666","last_name":"Frahm","first_name":"Björn"}],"volume":9,"publication_status":"published","date_created":"2024-04-25T13:34:26Z","language":[{"iso":"eng"}],"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>.","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","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>.","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).","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>","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>.","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>, .","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.","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>.","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).","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)."},"place":"Basel","title":"Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study","publication":"Processes","_id":"11376","article_number":"964","type":"scientific_journal_article","publisher":"MDPI AG","issue":"6","doi":"10.3390/pr9060964","date_updated":"2024-05-21T09:29:02Z","department":[{"_id":"DEP4000"}],"user_id":"83781","year":"2021","status":"public","keyword":["clonal cell population","phenotypic diversity","inoculum train","uncertainty-based","cell culture model","biopharmaceutical manufacturing"],"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."}]},{"keyword":["clonal cell population","phenotypic diversity","inoculum train","uncertainty-based","cell culture model","biopharmaceutical manufacturing"],"page":"49-74","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."}],"department":[{"_id":"DEP4021"}],"user_id":"83781","year":"2021","status":"public","quality_controlled":"1","doi":"10.3390/pr9060964","date_updated":"2023-08-16T09:17:50Z","type":"book_chapter","publisher":"MDPI","_id":"7983","series_title":"Processes : open access journal ","publication":"Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing","title":"Considerations of the impacts of cell-specific growth and production rate on clone selection – a simulation study","publication_identifier":{"eisbn":["978-3-0365-5209-5"],"issn":["2227-9717 "],"isbn":["978-3-0365-5210-1"]},"author":[{"last_name":"Hernández Rodriguez","id":"52466","full_name":"Hernández Rodriguez, Tanja","first_name":"Tanja"},{"full_name":"Morerod, Sophie","last_name":"Morerod","first_name":"Sophie"},{"full_name":"Pörtner, Ralf","last_name":"Pörtner","first_name":"Ralf"},{"full_name":"Wurm, Florian M.","last_name":"Wurm","first_name":"Florian M."},{"first_name":"Björn","full_name":"Frahm, Björn","last_name":"Frahm","id":"45666"}],"date_created":"2022-05-05T12:55:52Z","language":[{"iso":"eng"}],"publication_status":"published","volume":"special issue","place":"Basel","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.” In <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, special issue:49–74. Processes : Open Access Journal . Basel: MDPI, 2021. <a href=\"https://doi.org/10.3390/pr9060964\">https://doi.org/10.3390/pr9060964</a>.","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>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, <i>Processes : open access journal </i>. Bd. special issue. Basel : MDPI, 2021, S. 49–74","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>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, vol. special issue. Basel: MDPI, pp. 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).","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: <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>. Vol special issue. Processes : open access journal . MDPI; 2021:49-74. doi:<a href=\"https://doi.org/10.3390/pr9060964\">10.3390/pr9060964</a>","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 <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, vol. special issue, Basel: MDPI, 2021, pp. 49–74. 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. In: <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, special issue:49–74. Processes : open access journal . Basel: MDPI. doi:<a href=\"https://doi.org/10.3390/pr9060964\">10.3390/pr9060964</a>, .","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: o. Hg.: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, Band <i>special issue</i>, Basel 2021 (Processes : open access journal ),  S. 49–74.","mla":"Hernández Rodriguez, Tanja, et al. “Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection – a Simulation Study.” <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>, vol. special issue, MDPI, 2021, pp. 49–74, <a href=\"https://doi.org/10.3390/pr9060964\">https://doi.org/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. In <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing: Vol. special issue</i> (pp. 49–74). MDPI. <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, in: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, MDPI, Basel, 2021, pp. 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."}},{"keyword":["Bayes","Digital twin","Parameter estimation","Seed train","Uncertainty"],"abstract":[{"text":"Model-based concepts and simulation techniques in combination with digital tools emerge as a key to explore the full potential of biopharmaceutical production processes, which contain several challenging development and process steps. One of these steps is the time- and cost-intensive cell proliferation process (also called seed train) to increase cell number from cell thawing up to production scale. Challenges like complex cell metabolism, batch-to-batch variation, variabilities in cell behavior, and influences of changes in cultivation conditions necessitate adequate digital solutions to provide information about the current and near future process state to derive correct process decisions.\r\nFor this purpose digital seed train twins have proved to be efficient, which digitally display the time-dependent behavior of important process variables based on mathematical models, strategies, and adaption procedures.\r\nThis chapter will outline the needs for digitalization of seed trains, the construction of a digital seed train twin, the role of parameter estimation, and different statistical methods within this context, which are applicable to several problems in the field of bioprocessing. The results of a case study are presented to illustrate a Bayesian approach for parameter estimation and prediction of an industrial cell culture seed train for seed train digitalization.","lang":"eng"}],"page":"97–131","user_id":"83781","year":"2021","department":[{"_id":"DEP4021"}],"status":"public","doi":"https://doi.org/10.1007/10_2020_137","date_updated":"2023-08-16T06:48:35Z","quality_controlled":"1","type":"book_chapter","publisher":"Springer","editor":[{"first_name":"Christoph ","full_name":"Herwig, Christoph ","last_name":"Herwig"},{"first_name":"Ralf ","full_name":"Pörtner, Ralf ","last_name":"Pörtner"},{"full_name":"Möller, Johannes ","last_name":"Möller","first_name":"Johannes "}],"_id":"3349","series_title":"Advances in Biochemical Engineering/Biotechnology","publication":"Digital Twins Tools and Concepts for Smart Biomanufacturing","title":"Digital Seed Train Twins and Statistical Methods","intvolume":"       176","author":[{"full_name":"Hernández Rodriguez, Tanja","id":"52466","last_name":"Hernández Rodriguez","first_name":"Tanja"},{"id":"45666","last_name":"Frahm","full_name":"Frahm, Björn","first_name":"Björn"}],"publication_identifier":{"eissn":["1616-8542"],"issn":["0724-6145"],"isbn":["978-3-030-71659-2"],"eisbn":["978-3-030-71660-8"]},"place":"Berlin, Heidelberg","citation":{"havard":"T. Hernández Rodriguez, B. Frahm, Digital Seed Train Twins and Statistical Methods, in: C. Herwig, R. Pörtner, J. Möller (Eds.), Digital Twins Tools and Concepts for Smart Biomanufacturing, Springer, Berlin, Heidelberg, 2021: pp. 97–131.","ieee":"T. Hernández Rodriguez and B. Frahm, “Digital Seed Train Twins and Statistical Methods,” in <i>Digital Twins Tools and Concepts for Smart Biomanufacturing</i>, vol. 176, C. Herwig, R. Pörtner, and J. Möller, Eds. Berlin, Heidelberg: Springer, 2021, pp. 97–131. doi: <a href=\"https://doi.org/10.1007/10_2020_137\">https://doi.org/10.1007/10_2020_137</a>.","ama":"Hernández Rodriguez T, Frahm B. Digital Seed Train Twins and Statistical Methods. In: Herwig C, Pörtner R, Möller J, eds. <i>Digital Twins Tools and Concepts for Smart Biomanufacturing</i>. Vol 176. Advances in Biochemical Engineering/Biotechnology. Springer; 2021:97-131. doi:<a href=\"https://doi.org/10.1007/10_2020_137\">https://doi.org/10.1007/10_2020_137</a>","van":"Hernández Rodriguez T, Frahm B. Digital Seed Train Twins and Statistical Methods. In: Herwig C, Pörtner R, Möller J, editors. Digital Twins Tools and Concepts for Smart Biomanufacturing. Berlin, Heidelberg: Springer; 2021. p. 97–131. (Advances in Biochemical Engineering/Biotechnology; vol. 176).","bjps":"<b>Hernández Rodriguez T and Frahm B</b> (2021) Digital Seed Train Twins and Statistical Methods. In Herwig C, Pörtner R and Möller J (eds), <i>Digital Twins Tools and Concepts for Smart Biomanufacturing</i>, vol. 176. Berlin, Heidelberg: Springer, pp. 97–131.","short":"T. Hernández Rodriguez, B. Frahm, in: C. Herwig, R. Pörtner, J. Möller (Eds.), Digital Twins Tools and Concepts for Smart Biomanufacturing, Springer, Berlin, Heidelberg, 2021, pp. 97–131.","apa":"Hernández Rodriguez, T., &#38; Frahm, B. (2021). Digital Seed Train Twins and Statistical Methods. In C. Herwig, R. Pörtner, &#38; J. Möller (Eds.), <i>Digital Twins Tools and Concepts for Smart Biomanufacturing</i> (Vol. 176, pp. 97–131). Springer. <a href=\"https://doi.org/10.1007/10_2020_137\">https://doi.org/10.1007/10_2020_137</a>","mla":"Hernández Rodriguez, Tanja, and Björn Frahm. “Digital Seed Train Twins and Statistical Methods.” <i>Digital Twins Tools and Concepts for Smart Biomanufacturing</i>, edited by Christoph  Herwig et al., vol. 176, Springer, 2021, pp. 97–131, <a href=\"https://doi.org/10.1007/10_2020_137\">https://doi.org/10.1007/10_2020_137</a>.","din1505-2-1":"<span style=\"font-variant:small-caps;\">Hernández Rodriguez, Tanja</span> ; <span style=\"font-variant:small-caps;\">Frahm, Björn</span>: Digital Seed Train Twins and Statistical Methods. In: <span style=\"font-variant:small-caps;\">Herwig, C.</span> ; <span style=\"font-variant:small-caps;\">Pörtner, R.</span> ; <span style=\"font-variant:small-caps;\">Möller, J.</span> (Hrsg.): <i>Digital Twins Tools and Concepts for Smart Biomanufacturing</i>, <i>Advances in Biochemical Engineering/Biotechnology</i>. Bd. 176. Berlin, Heidelberg : Springer, 2021, S. 97–131","ufg":"<b>Hernández Rodriguez, Tanja/Frahm, Björn</b>: Digital Seed Train Twins and Statistical Methods, in: <i>Herwig, Christoph/Pörtner, Ralf/Möller, Johannes (Hgg.)</i>: Digital Twins Tools and Concepts for Smart Biomanufacturing, Bd. 176, Berlin, Heidelberg 2021 (Advances in Biochemical Engineering/Biotechnology),  S. 97–131.","chicago-de":"Hernández Rodriguez, Tanja und Björn Frahm. 2021. Digital Seed Train Twins and Statistical Methods. In: <i>Digital Twins Tools and Concepts for Smart Biomanufacturing</i>, hg. von Christoph  Herwig, Ralf  Pörtner, und Johannes  Möller, 176:97–131. Advances in Biochemical Engineering/Biotechnology. Berlin, Heidelberg: Springer. doi:<a href=\"https://doi.org/10.1007/10_2020_137\">https://doi.org/10.1007/10_2020_137</a>, .","chicago":"Hernández Rodriguez, Tanja, and Björn Frahm. “Digital Seed Train Twins and Statistical Methods.” In <i>Digital Twins Tools and Concepts for Smart Biomanufacturing</i>, edited by Christoph  Herwig, Ralf  Pörtner, and Johannes  Möller, 176:97–131. Advances in Biochemical Engineering/Biotechnology. Berlin, Heidelberg: Springer, 2021. <a href=\"https://doi.org/10.1007/10_2020_137\">https://doi.org/10.1007/10_2020_137</a>."},"language":[{"iso":"eng"}],"date_created":"2020-08-19T07:14:11Z","volume":176,"publication_status":"published"}]