Möller, JohannesJohannesMöllerHernández Rodríguez, TanjaTanjaHernández RodríguezMüller, JanJanMüllerArndt, LukasLukasArndtKuchemüller, Kim BeatriceKim BeatriceKuchemüllerFrahm, BjörnBjörnFrahmEibl, RegineRegineEiblEibl, DieterDieterEiblPörtner, RalfRalfPörtner2020-01-282020-01-282020-03-04Computers and Chemical Engineering (134): 106693 (2020-03-04)http://hdl.handle.net/11420/4596Reliable scale-up of biopharmaceutical production processes is key in Quality by Design. In this study, a model-based workflow is described to evaluate the bioprocess dynamics during process transfer and scale-up computationally. First, a mathematical model describes the bioprocess dynamics of different state variables (e.g., cell density, titer). Second, the model parameter probability distributions are de- termined at different scales due to measurement uncertainty. Third, the quantified parameter distribu- tions are statistically compared to evaluate if the process dynamics have been changed. This workflow was tested for the scale-up of an antibody-producing CHO fed-batch process. Significant differences were identified between the process development (30 ml) and implementation (250 ml) scale, and the feeding strategy was validated using model-assisted Design of Experiments. Then, the validated process strategy was successfully scaled up to 2 l laboratory and 50 l pilot scale. In summary, the proposed workflow enables a knowledge-driven evaluation tool for bioprocess development.en0098-13542020Elsevier Sciencehttps://creativecommons.org/licenses/by/4.0/Biowissenschaften, BiologieJournal Article10.15480/882.260010.1016/j.compchemeng.2019.10669310.15480/882.2600Journal Article