ABSTRACT
This chapter covers general aspects of upstream processing of cell culture‐based viral vaccine manufacturing. To this end, possible vaccine types are discussed and important steps to consider in the design of the manufacturing process are named, including the impact of downstream processing. The use of adherent versus suspension cells is discussed, considering cell attachment (also on microcarriers), passaging, cell banking as well as inoculum generation and establishment of a seed train. Available cell culture media are introduced, media components listed, and cell metabolism described. Furthermore, virus seed preparation and virus production is discussed, including the impact of defective interfering particles. Next, an introduction to cultivation vessels, such as static systems, classical stirred tank bioreactors and single‐use bioreactors is given. Scale‐up and manufacturing options are considered in a calculation exercise. Process parameters, like temperature, pH value, oxygen supply, stirring, shear stress, multiplicity of infection, time of infection and harvest are discussed. On‐line monitoring tools are addressed briefly. Decision criteria such as maximum virus titer and cell‐specific virus yield are introduced. Finally, biosafety considerations and a short introduction to good manufacturing practice including vaccine approval and market authorization are addressed.
