Optimization and Scale-Up of High Density Cell Culture Bioreactors

Abstract

High density cell culture systems offer more than a one-order of magnitude increase in reactor productivity. The design and scale-up of these systems are, however, more difficult. The challenges start with the mechanical design of the bioreactors; mixing and mass transfer are more critical in high density systems. In this paper, we analyze several methods of cell retention systems and discuss their operation. High density perfusion bioreactors can be operated in commercial scale production for more than 3 months at cell concentrations up to 10–40 million cells ml⁻¹. Optimization of these reactors involves altering feed rate and composition, reactor pH and DO. In some cases, local mass transfer gradients can also affect the cell physiology and increase cell specific productivity. This paper discusses our studies for industrial scale mammalian cell product development, optimization, and reactor scale-up.