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Digital Twins pp 1–28Cite as

Potential of Integrating Model-Based Design of Experiments Approaches and Process Analytical Technologies for Bioprocess Scale-Down

Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE,volume 177)

Abstract

Typically, bioprocesses on an industrial scale are dynamic systems with a certain degree of variability, system inhomogeneities, and even population heterogeneities. Therefore, the scaling of such processes from laboratory to industrial scale and vice versa is not a trivial task. Traditional scale-down methodologies consider several technical parameters, so that systems on the laboratory scale tend to qualitatively reflect large-scale effects, but not the dynamic situation in an industrial bioreactor over the entire process, from the perspective of a cell. Supported by the enormous increase in computing power, the latest scientific focus is on the application of dynamic models, in combination with computational fluid dynamics to quantitatively describe cell behavior. These models allow the description of possible cellular lifelines which in turn can be used to derive a regime analysis for scale-down experiments. However, the approaches described so far, which were for a very few process examples, are very labor- and time-intensive and cannot be validated easily. In parallel, alternatives have been developed based on the description of the industrial process with hybrid process models, which describe a process mechanistically as far as possible in order to determine the essential process parameters with their respective variances. On-line analytical methods allow the characterization of population heterogeneity directly in the process. This detailed information from the industrial process can be used in laboratory screening systems to select relevant conditions in which the cell and process related parameters reflect the situation in the industrial scale. In our opinion, these technologies, which are available in research for modeling biological systems, in combination with process analytical techniques are so far developed that they can be implemented in industrial routines for faster development of new processes and optimization of existing ones.

Graphical Abstract

Keywords

  • Bioprocess scale-up
  • Process analytical techniques
  • Process modeling
  • Scale-down

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Authors and Affiliations

  1. Bioprocess Engineering, Faculty III Process Sciences, Institute of Biotechnology, Technische Universität Berlin (TU Berlin), Berlin, Germany

    Peter Neubauer, Emmanuel Anane & Stefan Junne

  2. DataHow AG, Zurich, Switzerland

    Mariano Nicolas Cruz Bournazou

Authors
  1. Peter Neubauer
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  2. Emmanuel Anane
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  3. Stefan Junne
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  4. Mariano Nicolas Cruz Bournazou
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Corresponding author

Correspondence to Peter Neubauer .

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Editors and Affiliations

  1. Institute of Chemical, Environmental and Bioscience Engineering, Vienna University of Technology, Wien, Austria

    Prof. Christoph Herwig

  2. Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, Hamburg, Germany

    Prof. Dr. Ralf Pörtner

  3. Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, Hamburg, Germany

    Dr. Johannes Möller

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Neubauer, P., Anane, E., Junne, S., Cruz Bournazou, M.N. (2020). Potential of Integrating Model-Based Design of Experiments Approaches and Process Analytical Technologies for Bioprocess Scale-Down. In: Herwig, C., Pörtner, R., Möller, J. (eds) Digital Twins. Advances in Biochemical Engineering/Biotechnology, vol 177. Springer, Cham. https://doi.org/10.1007/10_2020_154

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