ABSTRACT
Fed-batch cultivation of mammalian cells is routinely used for industrial production of biologicals as a simple means of process intensification to increase cell concentration and to extend culture lifetime for a high product concentration and volumetric productivity. The operation is simple and sufficiently flexible to be implemented in existing facilities without major equipment modifications. However, its performance is strongly dependent upon the effectiveness of the nutrient feeding strategy to prevent nutrient depletion=accumulation and byproduct accumulation, so that critical nutritional and biochemical parameters including osmolality and carbon dioxide concentration can be maintained within levels suitable to promote cell growth or minimize cell death for product expression.
