, Volume 63, Issue 1, pp 41–47 | Cite as

Increasing batch-to-batch reproducibility of CHO cultures by robust open-loop control

  • M. Aehle
  • A. Kuprijanov
  • S. Schaepe
  • R. Simutis
  • A. LübbertEmail author
Original Research


In order to guarantee the quality of recombinant therapeutic proteins produced in mammalian cell systems, the straightforward approach in industry is to run the processes as reproducible as possible. It is first shown that considerable distortions in the currently operated processes appear when the initial cell density deviates from its nominal value. Small deviations in the initial cell mass may lead to severe deviations from the desired biomass trajectory. Next, it is shown how to design a fed-batch production process in such a way that it is robust with respect to variations in the viable cell density. A simple open loop strategy is proposed for that purpose. Here we show for the first time at animal cell cultures (CHO cells) that by means of an appropriate glutamine feed rate profile F(t), which keeps the specific growth rate of the cells on a predefined value below its maximal value while maintaining the viabilities on a high level, the diverging viable cell count profiles change over into a robust converging set of profiles. The CHO cells used to validate the procedure could be focused to any specific growth rates below μmax.


Mammalian cell culture Process reproducibility Open loop control Quality by design 



The financial support from the “Excellence Initiative” of the German federal state “Sachsen-Anhalt” is gratefully acknowledged.


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • M. Aehle
    • 1
  • A. Kuprijanov
    • 1
  • S. Schaepe
    • 1
  • R. Simutis
    • 2
  • A. Lübbert
    • 1
    Email author
  1. 1.Institute of Biochemistry and BiotechnologyMartin-Luther-University Halle-WittenbergHalle (Saale)Germany
  2. 2.Institute of Automation and Control SystemsKaunas University of TechnologyKaunasLithuania

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