title: The importance of formulation in the successful lyophilization of influenza reference materials.
abstract: Lyophilized Influenza antigen reference reagents are a critical resource in the quality control of influenza vaccines. A standard formulation has been used successfully at NIBSC for many years however, following the unexpected occurrence of a collapsed appearance in a particular batch a study was carried out to establish the impact of the sugar concentration in the formulation using modulated differential scanning calorimetry (mDSC) and nuclear magnetic resonance spectroscopy (NMR). There was a correlation between the presence and size of the mDSC eutectic temperature events and the freeze dried appearance of the cakes, which became progressively worse with increasing amounts of sugar. NMR spectroscopy could be used to positively identify and quantify the sugars in the formulations. MDSC can rapidly predict if the freeze dried appearance will be acceptable so as to assure the successful lyophilization of influenza reference preparations.
authors.affiliation: Standardisation Science, NIBSC, Medicines & Healthcare Products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK. Electronic address: chinwe.duru@nibsc.org.
authors.forename: Chinwe
authors.initials: C
authors.lastname: Duru
authors.affiliation: Laboratory of Molecular Structure, NIBSC, Medicines & Healthcare Products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK. Electronic address: carolyn.swann@nibsc.org.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Swann
authors.affiliation: Division of Virology, NIBSC, Medicines & Healthcare Products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK. Electronic address: una.dunleavy@nibsc.org.
authors.forename: Una
authors.initials: U
authors.lastname: Dunleavy
authors.affiliation: Laboratory of Molecular Structure, NIBSC, Medicines & Healthcare Products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK. Electronic address: b.mulloy@imperial.ac.uk.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mulloy
authors.affiliation: Standardisation Science, NIBSC, Medicines & Healthcare Products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK. Electronic address: paul.matejtschuk@nibsc.org.
authors.forename: Paul
authors.initials: P
authors.lastname: Matejtschuk
mesh_terms: D000956:Antigens, Viral / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods / Q000592:standards; D006801:Humans; D007252:Influenza Vaccines / Q000737:chemistry / Q000592:standards; D012015:Reference Standards
chemical_list: D000956:Antigens, Viral; D007252:Influenza Vaccines
keywords: DSC; Formulation; Influenza antigen; Lyophilization; NMR; PBS