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Decision tree for selection of suitable cultivation parameters for mammalian cell culture processes

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Background

Development of bioprocesses for mammalian cells has to deal with different bioreactor types and scales. Bio-reactors might be intended for seed train and production, research, process development, validation or transfer purposes. During these activities, not only the problem of up- and downscaling might lead to failure of repro-ducibility, but also the use of different bioreactor geometries and operation conditions. In such cases, the criteria for bioreactor design and process transfer should be re-evaluated in order to avoid an erroneous transfer of cultivation parameters.

Concept

For selection of process conditions several questions can be asked:

  • Type and scale of the intended cultivation system

  • Which data are required (cell specific parameters, specific data for the cultivation system)?

  • Are appropriate data e.g. for cell growth, substrate uptake, medium composition available?

  • For which cultivation systems have these data been determined?

  • Are data on power input, mixing time, oxygen transfer etc. available?

  • Which methods can be used to determine or estimate the above mentioned parameters?

For selection and evaluation of suitable cultivation parameters a decision tree (Figure 1) has been formulated to provide a guideline for design of mammalian cell culture processes. References for process transfer strategies are given for the following cases:

  • Scale similar and power imput similar: [13]

  • Scale similar and power imput similar: [46]

  • Scale up and power imput similar: [7, 8]

  • Scale up and power imput similar: [4, 9, 10]

Figure 1
figure1

Decision tree for selection of suitable cultivation parameters µ - growth rate, OTR - oxygen transfer rate, OUR - oxygen uptake rate, k L a - volume specific mass transfer coefficient.

References

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    Minow B, Seidemann J, Tschoepe S, Gloeckner A, Neubauer P: Harmonization and characterization of different single-use bioreactors adopting a new sparger design. Eng Life Sci. 2014, 14 (3): 272-282.

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    Kaiser St, Eibl D: Dynamic Single-Use Bioreactors Used in Modern Liter- and m3- Scale. Biotechnological Processes: Engineering Characteristics and Scaling Up.AdvBiochemEngBiotechnol. 2014, 138: 1-44.

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    Goedde A, Reiser S, Russ K, Krüger O, Cayli A, Wagner R: Characterisation of two Single-Use Bioreactors for Mammalian Cell Culture Processes. Oktober 2010, [http://rentschler.de/fileadmin/Downloads/Poster/Rentschler-Poster-BMD_Summit-2010.pdf]

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    Xing Z, Kenty BM, Li ZJ, Lee SS: Scale-up analysis for a CHO cell culture process in large-scale bioreactors. BiotechnolBioeng. 2009, 103 (4): 733-746.

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    Yang JD, Lu C, Stasny B, Henley J, Guinto W, Gonzalez C, et al: Fed-batch bioreactor process scale-up from 3-L to 2,500-L scale for monoclonal antibody production from cell culture. BiotechnolBioeng. 2007, 98 (1): 141-154.

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    Minow B, Rogge P, Thompson K: Implementing a Fully Disposable MAb Manufacturing Facility. 2012, [http://www.bioprocessintl.com/manufacturing/antibody-non-antibody/implementing-a-fully-disposable-mab-manufacturing-facility-331156/]

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    Minow B: Fast Track API Manufacturing in a 1000-L Single Use Facility Facilitating a Platform Process and a Simplified Scale-up Approach. JAACT 2012, Nagoya, Japan. 2012, 28. November 2012

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Author information

Correspondence to Ralf Pörtner.

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Keywords

  • Decision Tree
  • Cultivation System
  • Process Transfer
  • Power Input
  • Operation Condition