Bioreactors, Cell Culture, Commercial Production

Abstract

AbstractVarious recombinant proteins expressed by animal cells and secondary metabolites produced by plant cells have significantly increased the demand for high‐value‐added (mainly biopharmaceutical) products in recent years. Without doubt, large‐scale efficient production of these compounds is very important to meet market requirements. As animal cells and plant cells are more sensitive to culture conditions than microorganisms, their bioreactor culture technique is critical to reduce the production cost. In order to favor the desired functions of the cells and achieve cost‐effective large‐scale manufacture, it is necessary to optimize and control the bioreactor environment via operating variables. In this article, the characteristics of various types of cell culture bioreactors including stirred‐tank bioreactors, pneumatically agitated bioreactors, membrane bioreactors, packed and fluidized‐bed bioreactors, and wave bioreactors are discussed. Details of basic bioreactor design principles such as shear force, oxygen supply, and mixing are introduced. The effects of process variables including oxygen and mass transfer, fluid mixing, temperature, pH, and light irradiation on cell cultures are described. Bioreactor operation strategies for cell cultures are compared. For commercial production scale‐up, different criteria are considered and industrial large‐scale examples are also illustrated.