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


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.


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

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.


  1. 1.

    Platas OB, Jandt U, PhanLd M, Villanueva ME, Schaletzky M, Rath A, Freund S, Reichl U, Skerhutt E, Scholz S, Noll ThSandig V, Pörtner R, Zeng AP: Evaluation of criteria for bioreactor comparison and operation standardisation for mammalian cell culture. EngLifeSci. 2012, 12 (5): 518-528.

  2. 2.

    Minow B, Tschoepe S, Regner A, Populin M, Reiser S, Noack C, Neubauer : Biological performance of two different 1000 L single-use bioreactors applying a simple transfer approach. Eng Life Sci. 2014, 14 (3): 283-291.

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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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    Greller G, Eibl D: Single-use wave-mixed versus stirred bioreactors for insect-cell/BEVS-based protein expression at benchtop scale. Eng Life Sci. 2014, 14 (3): 264-271.

  6. 6.

    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, []

  7. 7.

    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.

  8. 8.

    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.

  9. 9.

    Minow B, Rogge P, Thompson K: Implementing a Fully Disposable MAb Manufacturing Facility. 2012, []

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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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Correspondence to Ralf Pörtner.

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Pörtner, R., Kern, S. & Eibl, D. Decision tree for selection of suitable cultivation parameters for mammalian cell culture processes. BMC Proc 9, P45 (2015).

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