title: Application of frequency-modulated spectroscopy in vacuum seal integrity testing of lyophilized biological products.
abstract: This study examined the feasibility of applying frequency-modulated spectroscopy (FMS) to test vacuum seal integrity of lyophilized protein pharmaceuticals in glass vials. A lyophilized recombinant monoclonal antibody was used as an example to demonstrate that FMS is a non-destructive method that could accurately and quickly determine vial vacuum integrity within a pressure range of 0.04 to 0.5 atm. The coefficient of determination (R2) of a bench-top instrument was found to be >0.99. Only seconds were required to analyze each sample. The instrument sensitivity and specificity were 0.95 and >0.99, respectively, based on analysis of approximately 40,000 samples. Because of low energy input by the instrument, no adverse effect on the protein quality was found immediately after up to 1 h of continuous laser exposure. The laser-exposed samples had comparable stability to non-exposed control vials after 12 weeks of storage at 40 degrees C.
authors.affiliation: Department of Pharmaceutical R&D.,Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Tanya P
authors.initials: TP
authors.lastname: Lin
authors.forename: Chung C
authors.initials: CC
authors.lastname: Hsu
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Kabakoff
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Patapoff
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D004349:Drug Packaging / Q000379:methods / Q000592:standards*; D004355:Drug Stability; D004356:Drug Storage; D005612:Freeze Drying; D012680:Sensitivity and Specificity; D017550:Spectroscopy, Fourier Transform Infrared; D014618:Vacuum
chemical_list: D000911:Antibodies, Monoclonal