title: Stabilization of HAC1 influenza vaccine by spray drying: formulation development and process scale-up.
abstract: OBJECTIVE
  Stable vaccines with long shelf lives and reduced dependency on the cold chain are ideal for stockpiling and rapid deployment during public emergencies, including pandemics. Spray drying is a low-cost process that has potential to produce vaccines stable at a wide range of temperatures. Our aim was to develop a stable formulation of a recombinant H1N1 influenza hemagglutinin vaccine candidate and take it to pilot-scale spray-drying production.
  
  
  METHODS
  Eight formulations containing different excipients were produced and assayed for antigen stability, powder characteristics, and immunogenicity after storage at a range of temperatures, resulting in the identification of four promising candidates. A pilot-scale spray-drying process was then developed for further testing of one formulation.
  
  
  RESULTS
  The pilot-scale process was used to reproducibly manufacture three batches of the selected formulation with yields >90%. All batches had stable physical properties and in vitro potency for 6 months at temperatures from -20°C to +50°C. Formulations stored for 3 months elicited immunogenic responses in mice equivalent to a frozen lot of bulk vaccine used as a stability control.
  
  
  CONCLUSIONS
  This study demonstrates the feasibility of stabilizing subunit vaccines using a spray-drying process and the suitability of the process for manufacturing a candidate product.
authors.affiliation: PATH, PO Box 900922, Seattle, Washington, 98109, USA.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhu
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shoji
authors.forename: Scott
authors.initials: S
authors.lastname: McCray
authors.forename: Michael
authors.initials: M
authors.lastname: Burke
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Hartman
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: Jeff
authors.initials: J
authors.lastname: Breit
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
authors.forename: Dexiang
authors.initials: D
authors.lastname: Chen
authors.forename: Manjari
authors.initials: M
authors.lastname: Lal
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000737:chemistry* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011208:Powders / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D000956:Antigens, Viral; D005079:Excipients; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011208:Powders