caa a22 4500 445822902 CHVBK 20180317145249.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s10616-010-9320-y doi (NATIONALLICENCE)springer-10.1007/s10616-010-9320-y Increasing batch-to-batch reproducibility of CHO cultures by robust open-loop control [Elektronische Daten] [M. Aehle, A. Kuprijanov, S. Schaepe, R. Simutis, A. Lübbert] 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. Springer Science+Business Media B.V., 2010 Mammalian cell culture nationallicence Process reproducibility nationallicence Open loop control nationallicence Quality by design nationallicence Aehle M. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany aut Kuprijanov A. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany aut Schaepe S. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany aut Simutis R. Institute of Automation and Control Systems, Kaunas University of Technology, Studentu g. 48, 3028, Kaunas, Lithuania aut Lübbert A. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany aut Cytotechnology Springer Netherlands 63/1(2011-01-01), 41-47 0920-9069 63:1<41 2011 63 10616 https://doi.org/10.1007/s10616-010-9320-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10616-010-9320-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Aehle M. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany aut NATIONALLICENCE 700 1- Kuprijanov A. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany aut NATIONALLICENCE 700 1- Schaepe S. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany aut NATIONALLICENCE 700 1- Simutis R. Institute of Automation and Control Systems, Kaunas University of Technology, Studentu g. 48, 3028, Kaunas, Lithuania aut NATIONALLICENCE 700 1- Lübbert A. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany aut NATIONALLICENCE 773 0- Cytotechnology Springer Netherlands 63/1(2011-01-01), 41-47 0920-9069 63:1<41 2011 63 10616 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer