Sensitive and spatially-selective quantification of oxygen in the headspace of pharmaceutical vials

Project Summary/AbstractPhysical Sciences Inc. (PSI) is developing a head space analyzer (HSA) to accurately measure 0.01% of O2 in the head space of pharmaceutical vials at a speed of 600 vials per minute. The measurement approach is non-destructive and selectively measures only oxygen in the vial head space. HSA is used in the pharmaceutical industry to evaluate the closed container integrity (CCI) of packaging against air ingress. The presence of oxygen in the head space indicates compromised packaging of a drug product, potentially reducing the shelf life and efficacy and voiding the sterility. This is particularly true for biologic drugs, the fastest growing pharmaceutical market segment valued at $90B/year, that are highly susceptible to oxygen-induced degradation. The current standard for non-destructive HSA is based on laser absorption spectroscopy. Laser-based HSA requires an active nitrogen purge to mitigate the signal contribution of ~20% oxygen present in room air. The reliability of head space measurements with laser- based HSA critically relies on the efficacy of a nitrogen purge. PSI's proposed HSA approach does not require a nitrogen purge removing a mode of failure, and will be an order of magnitude more sensitive than conventional laser-based HSAs. More sensitive detection of oxygen will lead to improved product shelf-life and a reduction in the shortages of biologics and other classes of drugs that are vulnerable to oxidation.During the Phase I program PSI will demonstrate the feasibility of the new HSA approach in a series of benchtop experiments with standard pharmaceutical vials of different sizes. These studies will demonstrate the capability of the technology to selectively quantify oxygen to 0.01% levels in the vial head space with detection limits better than what are achieved with conventional laser-based HSAs. The experimental studies will also demonstrate the capability of the HSA approach to be operated without an active nitrogen purge. Knowledge gained from the Phase I studies will guide the development of a fieldable prototype design to be fabricated during the Phase II program. In the Phase I program PSI will establish a collaboration with a company that manufactures and sells vial inspection instrumentation. The industry collaborator will provide a location for field testing of a prototype system fabricated in the Phase II program.