Influence of operating parameters of a settling-based perfusion process on expansion of VERO cells attached on microcarriers

Background The growing demand for biologicals produced by animal cells motivates the development of more efficient and reliable culture production processes. In the particular case of the industrial production of viral vaccines by Vero cells adhered on microcarriers, the cell propagation phases are mainly devoted to reach high cell density in less time while maintaining a good cell physiological state. Several papers have reported the optimization of culture conditions for microcarrier cultures [1-4]. Otherwise, perfusion bioreactors, based on continuous medium renewal and cell retention, can be a good alternative to batch systems. Among the various technologies for cell retention, gravitational settler is a promising device for large-scale perfusion culture process. This simple device takes advantage of the difference between the cell settling rate and the medium harvesting flow rate. Moreover, in the particular case of cells attached on microcarriers, it is more suitable than in the case of single suspended cells. So, the aim of this work was to evaluate the performances of adherent Vero cell cultures performed inside a perfused bioreactor using a gravitational settler as cell retention device. The study focused on the influence of two operating parameters, such as microcarrier concentration (MCs) and initial cell density (C0), on the cell growth.