It is widely recognized in the biopharmaceutical community that a thorough evaluation of the design space is imperative in the current regulatory environment. Perfusion cultivation of mammalian cells has the advantages of high cell density and viability over the course of long cultivation periods and is especially suited for labile molecules because it allows retention time control by the adjustment of perfusion rate. This study is focused on the evaluation of the design space in a perfusion system. First, a risk analysis was performed to determine the critical and key parameters in a perfusion system. This was followed by a demonstration that a laboratory-scale perfusion system was a good scaled-down representation of the manufacturing system. Subsequently, a full factorial design was used to examine the design space for critical parameters in the laboratory-scale system. In addition to typical cell culture parameters, product quality attributes were measured for each experimental condition resulting in a comprehensive data set of response variables. Finally, response surface analysis was used to examine the relationship between critical parameters and the cell culture and product quality attributes of interest resulting in a well characterized design space for the perfusion system.

Design space studies for high-density perfusion cultivation of mammalian cells

239th National Meeting (2010)

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