title: Clarification of vaccines: An overview of filter based technology trends and best practices.
abstract: Vaccines are derived from a variety of sources including tissue extracts, bacterial cells, virus particles, recombinant mammalian, yeast and insect cell produced proteins and nucleic acids. The most common method of vaccine production is based on an initial fermentation process followed by purification. Production of vaccines is a complex process involving many different steps and processes. Selection of the appropriate purification method is critical to achieving desired purity of the final product. Clarification of vaccines is a critical step that strongly impacts product recovery and subsequent downstream purification. There are several technologies that can be applied for vaccine clarification. Selection of a harvesting method and equipment depends on the type of cells, product being harvested, and properties of the process fluids. These techniques include membrane filtration (microfiltration, tangential-flow filtration), centrifugation, and depth filtration (normal flow filtration). Historically vaccine harvest clarification was usually achieved by centrifugation followed by depth filtration. Recently membrane based technologies have gained prominence in vaccine clarification. The increasing use of single-use technologies in upstream processes necessitated a shift in harvest strategies. This review offers a comprehensive view on different membrane based technologies and their application in vaccine clarification, outlines the challenges involved and presents the current state of best practices in the clarification of vaccines.
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Besnard
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Fabre
authors.affiliation: EMD Millipore Corporation, 900 Middlesex Turnpike, Billerica, MA 00000, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Fettig
authors.affiliation: EMD Millipore, 109 Woodbine Downs Blvd., Unit 5, Toronto, ON M9W 6Y1, Canada.
authors.forename: Elina
authors.initials: E
authors.lastname: Gousseinov
authors.affiliation: Merck Ltd., DiverCity Tokyo Office Tower 15F, 1-1-20 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Millipore S.A.S., Rue J. Monod, 78280 Guyancourt, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Laroudie
authors.affiliation: EMD Millipore Corporation, 900 Middlesex Turnpike, Billerica, MA 00000, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Scanlan
authors.affiliation: Merck Pte Ltd., 1 Science Park Road, #02-10/11 The Capricorn, 117528, Singapore, Singapore. Electronic address: priyabrata.pattnaik@merckgroup.com.
authors.forename: Priyabrata
authors.initials: P
authors.lastname: Pattnaik
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000302:isolation & purification; D001709:Biotechnology / Q000379:methods*; D002498:Centrifugation / Q000379:methods; D002642:Chick Embryo / Q000821:virology; D005285:Fermentation; D005374:Filtration / Q000379:methods; D022242:Pneumococcal Vaccines / Q000302:isolation & purification; D013744:Tetanus Toxin / Q000302:isolation & purification; D014121:Toxoids; D014612:Vaccines; D019444:Vaccines, DNA / Q000302:isolation & purification; D014765:Viral Vaccines / Q000302:isolation & purification
chemical_list: D001428:Bacterial Vaccines; D022242:Pneumococcal Vaccines; D013744:Tetanus Toxin; D014121:Toxoids; D014612:Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines
keywords: Bacterial vaccine; Clarification; Conjugated polysaccharide vaccine; Filtration; Harvest; Normal flow filtration; Purification; Tangential flow filtration; Vaccine; Viral vaccine