title: Freeze-drying of live virus vaccines: A review.
abstract: Freeze-drying is the preferred method for stabilizing live, attenuated virus vaccines. After decades of research on several aspects of the process like the stabilization and destabilization mechanisms of the live, attenuated viruses during freeze-drying, the optimal formulation components and process settings are still matter of research. The molecular complexity of live, attenuated viruses, the multiple destabilization pathways and the lack of analytical techniques allowing the measurement of physicochemical changes in the antigen's structure during and after freeze-drying mean that they form a particular lyophilization challenge. The purpose of this review is to overview the available information on the development of the freeze-drying process of live, attenuated virus vaccines, herewith focusing on the freezing and drying stresses the viruses can undergo during processing as well as on the mechanisms and strategies (formulation and process) that are used to stabilize them during freeze-drying.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
authors.forename: L J J
authors.initials: LJJ
authors.lastname: Hansen
authors.affiliation: Zoetis, Hoge Wei 10, Zaventem 1930, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Daoussi
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
authors.forename: J-P
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium. Electronic address: Thomas.debeer@Ugent.be.
authors.forename: T R M
authors.initials: TRM
authors.lastname: De Beer
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D003451:Cryoprotective Agents / Q000737:chemistry; D005612:Freeze Drying / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007053:Ice; D009994:Osmolar Concentration; D013678:Technology, Pharmaceutical; D014613:Vaccines, Attenuated / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry; D014765:Viral Vaccines / Q000737:chemistry*
chemical_list: D003451:Cryoprotective Agents; D007053:Ice; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D014765:Viral Vaccines
keywords: Design of a formulation; Live, attenuated virus; Lyophilization; Stabilization of viruses