title: Bioreactor concepts for cell culture-based viral vaccine production.
abstract: Vaccine manufacturing processes are designed to meet present and upcoming challenges associated with a growing vaccine market and to include multi-use facilities offering a broad portfolio and faster reaction times in case of pandemics and emerging diseases. The final products, from whole viruses to recombinant viral proteins, are very diverse, making standard process strategies hardly universally applicable. Numerous factors such as cell substrate, virus strain or expression system, medium, cultivation system, cultivation method, and scale need consideration. Reviewing options for efficient and economical production of human vaccines, this paper discusses basic factors relevant for viral antigen production in mammalian cells, avian cells and insect cells. In addition, bioreactor concepts, including static systems, single-use systems, stirred tanks and packed-beds are addressed. On this basis, methods towards process intensification, in particular operational strategies, the use of perfusion systems for high product yields, and steps to establish continuous processes are introduced.
authors.affiliation: Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, Magdeburg; Sandtorstr. 1, 39106 Magdeburg, Germany.
authors.forename: Lilí Esmeralda
authors.initials: LE
authors.lastname: Gallo-Ramírez
authors.forename: Alexander
authors.initials: A
authors.lastname: Nikolay
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Genzel
authors.forename: Udo
authors.initials: U
authors.lastname: Reichl
mesh_terms: D000818:Animals; D019149:Bioreactors; D001717:Birds; D018929:Cell Culture Techniques; D007313:Insecta; D008322:Mammals; D013678:Technology, Pharmaceutical / Q000379:methods*; D014765:Viral Vaccines / Q000302:isolation & purification*; D014776:Virus Cultivation / Q000379:methods*
chemical_list: D014765:Viral Vaccines
keywords: animal cell culture; bioreactor systems; continuous processes; large-scale vaccine production; process improvement; process intensification; viral vaccines