RT Journal Article SR Electronic T1 Application of Frequency-Modulated Spectroscopy in Vacuum Seal Integrity Testing of Lyophilized Biological Products JF PDA Journal of Pharmaceutical Science and Technology JO PDA J Pharm Sci Technol FD Parenteral Drug Association (PDA) SP 106 OP 115 VO 58 IS 2 A1 Tanya P. Lin A1 Chung C. Hsu A1 Bruce D. Kabakoff A1 Thomas W. Patapoff YR 2004 UL http://journal.pda.org/content/58/2/106.abstract AB 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°C.