Scale‐Up and Scale‐Down Methodologies for Bioreactors

Scale-up is usually complicated by the fact that bioprocesses in general are gas–liquid systems, whereby the liquid phase also includes the specific biological component, which is the living cell itself. In addition, in most cases, several liquid feed streams are supplied in continuous or discontinuous mode to the bioreactor, such as glucose and one or two pH-adjusting agents, with the aim to control certain process parameters. Most importantly, the chemical and physical (density, viscosity of the broth) composition of the liquid and gas phases changes over time due to the consumption or secretion of chemical molecules by the biological system. This in turn influences the fluid dynamics and leads to gradient formation, which was proven to have an impact on the process performance in the industrial scale. In order to examine the consequences in smaller scale, scale-down reactor systems have been applied. This chapter aims to describe the interdisciplinary methods, which have been developed to perform scale-down studies to mimic the industrial scale as close as feasible, and to summarize the outcomes and conclusions of these studies for a suitable process development procedure and large-scale operation.