title: Challenges in manufacturing adenoviral vectors for global vaccine product deployment.
abstract: Abstract Once adenovirus vector-based vaccines are licensed for the prevention of important infectious diseases, manufacturing processes capable of reliably delivering large numbers of vaccine doses will be required. The highest burden of disease for many infectious pathogens under investigation occurs in resource-poor settings. Therefore, the price per dose will be an important determinant of success. This review describes common practices for manufacturing replication-incompetent adenovirus vectors at clinical scale. Recent innovations and strategies aimed at improving the cost-effectiveness of manufacturing and ensuring high-volume vaccine production and purification are described. Hereto, technologies to increase bioreactor yields are reviewed. In addition, the use of single-use perfusion bioreactors, modification of some purification steps to avoid the use of expensive endonucleases, and use of charged filters during anion exchange all have the potential to bring down the cost of goods and are thus described. Finally, processes for ensuring quality throughout the manufacturing process, methods for testing viral identity, and safety of master seeds through to the end vaccine product are described.
authors.affiliation: 1 Crucell Holland BV , 2333CN Leiden, The Netherlands .
authors.forename: Jort
authors.initials: J
authors.lastname: Vellinga
authors.forename: J Patrick
authors.initials: JP
authors.lastname: Smith
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lipiec
authors.forename: Dragomira
authors.initials: D
authors.lastname: Majhen
authors.forename: Angelique
authors.initials: A
authors.lastname: Lemckert
authors.forename: Mark
authors.initials: M
authors.lastname: van Ooij
authors.forename: Paul
authors.initials: P
authors.lastname: Ives
authors.forename: Christopher
authors.initials: C
authors.lastname: Yallop
authors.forename: Jerome
authors.initials: J
authors.lastname: Custers
authors.forename: Menzo
authors.initials: M
authors.lastname: Havenga
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D019149:Bioreactors; D001709:Biotechnology / Q000379:methods / Q000592:standards; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology; D006801:Humans; D014614:Vaccines, Synthetic / Q000235:genetics* / Q000276:immunology
chemical_list: D014614:Vaccines, Synthetic