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Keywords:

  • animal cell kinetics;
  • bioreactor;
  • mammalian cells;
  • mathematical modelling;
  • monoclonal antibodies;
  • sensitivity analysis

Animal cell culture is widely used in the manufacture of valuable products, and this process is nowadays seeing a rapid expansion. The growth of animal cells is a complex process, because the cells are very sensitive to environmental changes (in, for example, nutrients, pH, temperature, oxygen and osmolarity) during this phase and to the toxic compounds produced by the cell itself. Ammonia and lactate are the two major waste materials of cell culture. They can have inhibitory effects on cell growth and product (monoclonal antibodies among others) formation. In order to model the behaviour of a fed-batch animal cell bioreactor producing monoclonal antibodies, it is necessary to use a complex kinetic model with optimal operating patterns ensuring high productivities. Good knowledge of such domains of operating parameters, together with the understanding of the response of this rather complex system to small modifications in the working conditions, are essential for on-line control to improve the quality of product and the yield of an animal cell culture. The present study focuses on the sensitivity analysis of a fed-batch animal cell bioreactor with respect to some candidate control parameters (substrate set-point concentrations, feeding time-step patterns and concentration of feeding solutions), emphasizing the influence of these on the overall performance of the system.