PT  - JOURNAL ARTICLE
AU  - Lin, Tanya P.
AU  - Hsu, Chung C.
AU  - Kabakoff, Bruce D.
AU  - Patapoff, Thomas W.
TI  - Application of Frequency-Modulated Spectroscopy in Vacuum Seal Integrity Testing of Lyophilized Biological Products
DP  - 2004 Mar 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 106--115
VI  - 58
IP  - 2
4099  - http://journal.pda.org/content/58/2/106.short
4100  - http://journal.pda.org/content/58/2/106.full
SO  - PDA J Pharm Sci Technol2004 Mar 01; 58
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.