Mammalian Fed‐batch Cell Culture for Biopharmaceuticals

The majority of the recombinant protein therapeutics on the market are currently produced using mammalian cell culture. This chapter introduces two common modes of mammalian cell culture, batch and fed-batch. Fed-batch cell culture is significantly more complex than batch culture because of the timing, amount, and dosage of the additional nutrient supplementation. Improving nutrient supplementation also results in higher cell mass, so there are also process variable design considerations, such as temperature, pH, dissolved oxygen, and culture duration. We discuss strategies for developing a fed-batch process, such as feed regime, feed media, process variables, supplements, and the potential effects that these process design choices can have on the main objectives of fed-batch cell culture: yield and protein product quality. Finally, we conclude with a brief discussion of new and emerging technologies in fed-batch cell culture that can further enhance biopharmaceutical yield, product quality, and capacity.