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Abstract

Since several years the cultivation of animal cells to produce complex proteins and vaccines is used in biotechnology. Due to enormous economical importance of infectious diseases, the difficulty in controling existing or up-coming infection risks and the potential of a treatment of cancer or autoimmune diseases, the development and optimization of new vaccines is still in the center of todays research. The aim of our work group is the development and optimization of integrated concepts to design and control vaccine production processes for the amelioration of viral yield and purity in conjunction with efficiency and safety of the vaccine. With a process of influenza virus vaccine production as an example we focus on the following steps: Fermentation and scale-up of animal cells (MDCK) using microcarrier-systems Replication of influenza viruses in MDCK cells Downstream Processing to a commercial vaccine In chemical engineering mathematical models for the description of reaction courses and optimization of processes are widely used. However, for biological systems not all underlying mechanisms are known, making a detailed description of all relevant cellular reaction steps impossible.One of our main interests is thus the presentation of a not too complex mathematical model, which describes the growth of adherent cells, virus replication and essential metabolism and regulation-steps (structured, non-segregated model). Using this model together with experiments in fermenters or single-cell cultures and determination of on- and off-line values used in industrial production processes should allow us to develop concepts for process monitoring and control. These concepts could then facilitate improvement and validation of these processes.