title: Technology transfer and scale-up of the Flublok recombinant hemagglutinin (HA) influenza vaccine manufacturing process.
abstract: Multiple different hemagglutinin (HA) protein antigens have been reproducibly manufactured at the 650L scale by Protein Sciences Corporation (PSC) based on an insect cell culture with baculovirus infection. Significantly, these HA protein antigens were produced by the same Universal Manufacturing process as described in the biological license application (BLA) for the first recombinant influenza vaccine approved by the FDA (Flublok). The technology is uniquely designed so that a change in vaccine composition can be readily accommodated from one HA protein antigen to another one. Here we present a vaccine candidate to combat the recently emerged H7N9 virus as an example starting with the genetic sequence for the required HA, creation of the baculovirus and ending with purified protein antigen (or vaccine component) at the 10L scale accomplished within 38 days under GMP conditions. The same process performance is being achieved at the 2L, 10L, 100L, 650L and 2500L scale. An illustration is given of how the technology was transferred from the benchmark 650L scale facility to a retrofitted microbial facility at the 2500L scale within 100 days which includes the time for facility engineering changes. The successful development, technology transfer and scale-up of the Flublok process has major implications for being ready to make vaccine rapidly on a worldwide scale as a defense against pandemic influenza. The technology described does not have the same vulnerability to mutations in the egg adapted strain, and resulting loss in vaccine efficacy, faced by egg based manufacture.
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA; Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK. Electronic address: buckland@biologicb.com.
authors.forename: Barry
authors.initials: B
authors.lastname: Buckland
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Boulanger
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
authors.forename: Mireli
authors.initials: M
authors.lastname: Fino
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
authors.forename: Indresh
authors.initials: I
authors.lastname: Srivastava
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Holtz
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Khramtsov
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
authors.forename: Clifton
authors.initials: C
authors.lastname: McPherson
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
authors.forename: Jamal
authors.initials: J
authors.lastname: Meghrous
authors.affiliation: ABEC Corporation, Bethlehem, PA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Kubera
authors.affiliation: Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
authors.forename: Manon M J
authors.initials: MM
authors.lastname: Cox
mesh_terms: D000818:Animals; D016367:Baculoviridae; D019149:Bioreactors; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000096:biosynthesis* / Q000302:isolation & purification; D064766:Influenza A Virus, H7N9 Subtype; D007252:Influenza Vaccines / Q000737:chemistry*; D007313:Insecta / Q000166:cytology; D011994:Recombinant Proteins / Q000276:immunology; D018581:Technology Transfer; D014614:Vaccines, Synthetic / Q000737:chemistry
chemical_list: C528512:FluBlok; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic
keywords: Flublok(®); H7N9; Influenza vaccine; Insect cell; Pandemic; Recombinant HA; Scale-up