Evolution and design of continuous bioreactors for the production of biological products

The bioprocessing industry is undergoing a crucial change from batch to continuous processes, backed by possible cost reductions and advantages in terms of stable product quality. Initially in this chapter, the concepts related to the birth of biotechnology are brought forward as well as some considerations related to selection of a suitable cell line depending on product type. Then, the three basic process modes for stirred tank bioreactors (i.e., batch, fed-batch and chemostat/CSTR) are exposed, including the mathematical expressions which can be used to model these processes. Perfusion-based continuous bioreactors are introduced as a way for achieving higher cell densities and therefore increasing productivities. Strategies for the development of these processes are explained, including the use of scale-down models. Finally, two case studies are brought forward. Firstly, the extracellular production of monoclonal antibodies, a rapidly expanding class of biopharmaceuticals. Secondly, the production of intracellular products via perfusion is exemplified with the case of bioplastics, specifically polyhydroxyalkanoates, one of the most researched biodegradable biopolymer.