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

项目摘要/摘要 物理科学公司(PSI)正在开发一种顶空分析仪(HSA)，可以准确地测量0.01% 以每分钟600瓶的速度在药瓶的顶部空间中释放氧气。测量 该方法是非破坏性的，只有选择地测量瓶头空间中的氧气。人血清白蛋白用于 制药行业评估包装对空气的封闭容器完整性(CCI) 入口。头部空间中氧气的存在表明药品的包装受损， 潜在地降低了保质期和有效性，并消除了无菌现象。对于生物学来说，这一点尤其正确 药品是增长最快的药品市场，每年价值900亿美元，非常容易受到影响 到氧气诱导的降解。目前的非破坏性人血清白蛋白标准是基于激光的。 吸收光谱学基于激光的人血清白蛋白需要主动氮气净化来缓解信号 房间空气中存在的~20%氧气的贡献。用激光测量头部空间的可靠性- 人血清白蛋白在很大程度上取决于氮气净化的效果。PSI提出的HSA方法没有 需要氮气吹扫消除一种故障模式，并且将比 传统的基于激光的HSA。更灵敏的氧气检测将延长产品的保质期 以及减少易受氧化的生物制品和其他类别药物的短缺。 在第一阶段计划期间，PSI将在一系列项目中展示新HSA方法的可行性 用不同大小的标准药瓶进行台式实验。这些研究将 展示了该技术选择性地将瓶头中的氧气定量到0.01%水平的能力 具有探测极限的空间比传统的基于激光的HSA所实现的更好。这个 实验研究还将证明人血清白蛋白方法能够在没有 主动氮气净化。从第一阶段研究中获得的知识将指导制定 将在第二阶段计划期间制作的可现场原型设计。在第一阶段计划中，PSI将 与制造和销售瓶子检测仪器的公司建立合作关系。这个 行业合作者将为在第二阶段制造的原型系统提供现场测试地点 程序。

Project Summary/Abstract Physical 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.