Model uncertainty-based evaluation of process strategies during scale-up of biopharmaceutical processes

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Autor/in:
Verlag/Körperschaft:
Hamburg University of Technology
Erscheinungsjahr:
2020
Medientyp:
Text
Schlagwort:
  • 570: Biowissenschaften, Biologie
Beschreibung:
  • Reliable 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. ©2020 Elsevier Ltd. All rights reserved.
Beziehungen:
DOI 10.1016/j.compchemeng.2019.106693
Lizenzen:
  • info:eu-repo/semantics/openAccess
  • https://creativecommons.org/licenses/by/4.0/
Quellsystem:
TUHH Open Research
Interne Metadaten
Quelldatensatz
oai:tore.tuhh.de:11420/4596