(457d) Development of a Robust Process for Harvesting Bioreactors

Analysis of significant factors that impact bioreactor cell culture growth and productivity was performed. Using fresh cell culture samples removed during bioreactor runs, we incorporated a new technique using a shear device to evaluate the timing of cell culture harvest in primary recovery. Our results show that cells become increasingly sensitive to shear with age in the bioreactor. Industry bioreactor operations typically have an established day for harvest normally based on bioreactor performance. However to optimize harvesting and clarification, for example, by centrifugation and filtration, it may be beneficial to harvest cultures when product has been optimized and before the cells become excessively sensitive to shear. The former condition may lead to unacceptable fouling of clarifying filters.