Year: 2010-11

Company: Gilead Sciences

Liaison(s): Gerald Jensen, Linda SooHoo, Tarquinus Bunch, Jack Kennavane, Catherine Kuo

Gilead Sciences, Inc. is a worldwide pharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet need. One important Gilead product is Cayston® (aztreonam), a monobactam antibiotic. This antibiotic is used in cystic fibrosis patients with respiratory problems resulting from Pseudomonas aeruginosa infections. Cayston® is supplied as a lyophilized cake which must be resuspended in saline and administered through a nebulizer. In order to reliably manufacture Cayston®, it is critical that moisture levels be held below 3%. Our project revolves around the development and implementation of a new method to determine the moisture content for Cayston®. The current “gold standard” method for measuring moisture content in lyophilized cakes is the Karl Fischer (KF) titration method. Unfortunately, the KF method is a difficult assay to perform and destroys the sample being tested. An alternative method uses NIR (near-infrared spectroscopy). The goal of our project was to conduct pre-validation studies in support of Gilead’s plans to demonstrate to the FDA that a NIR based method demonstrates analytical equivalence to the established KF method. In support of that goal, we examined rotational and temperature effect s as well as precision, repeatability, and robustness using lyophilized cakes of Cayston®. Finally, we developed a standard curve and examined the accuracy of the NIRS assay compared to the “gold standard” KF assay. The results of these studies will be used to write an SOP (standard operating procedure) for the operation of the NIR instrument as well as the detailed instructions for Cayston® sample analysis. This work will be used to provide the framework for a formal study Gilead will perform to demonstrate that NIR spectroscopy is an acceptable substitute to the KF method for the accurate measurement of percent moisture in lyophilized cakes of Cayston®.