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

对药瓶顶部空间的氧气进行灵敏且空间选择性的定量

• 批准号: 10545821
• 负责人: Brian E Brumfield
• 金额: $ 26.3万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545821
• 关键词: Air; Atmospheric Pressure; Biological; Biological Products; Collaborations; Detection; Development; Device or Instrument Development; Drug Design; Drug Industry; Drug Kinetics; Drug Packaging; Ensure; Evaluation; Failure; Frequencies; Gases; Generations; Government; Head; Industry Collaboration; Injections; Intravenous; Knowledge; Lasers; Life; Location; Magnetism; Measurement; Measures; Methods; Monitor; Nitrogen; Oxygen; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Predisposition; Research; Rotation; Series; Signal Transduction; Spectrum Analysis; Speed; Sterility; System; Techniques; Technology; Testing; Vacuum; Validation; Vial device; absorption; air monitoring; base; design; detection limit; detection platform; experimental study; field study; immunogenicity; improved; instrument; instrumentation; magnetic field; oxidation; parity; phase 1 study; physical science; preservation; prevent; programs; prototype; purge; research and development; seal; sensor; temporal measurement

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.

项目总结/摘要 物理科学公司(PSI)正在开发一种顶空分析仪（HSA）， 在药瓶的顶部空间中以每分钟600个药瓶的速度释放氧气。测量 该方法是非破坏性的，并且仅选择性地测量小瓶顶部空间中的氧气。HSA用于 制药行业评估包装的密闭容器完整性（CCI） 入口。顶部空间中氧气的存在表明药物产品的包装受损， 潜在地降低了保存期和功效并使无菌性失效。生物学尤其如此。 药物，增长最快的医药市场，价值900亿美元/年，是高度敏感的 氧气引起的降解。目前的非破坏性HSA标准是基于激光 吸收光谱学基于激光的HSA需要主动氮气吹扫以减轻信号 室内空气中存在约20%的氧气。激光顶空测量的可靠性- 的HSA严重依赖于氮气吹扫的功效。PSI提出的HSA方法并不 需要氮气吹扫，以消除故障模式，并且将比 传统的基于激光的HSA。更灵敏的氧气检测将提高产品的保质期 以及减少生物制剂和其他易受氧化影响的药物的短缺。 在第一阶段计划中，PSI将通过一系列的实验来证明新的HSA方法的可行性。 使用不同尺寸的标准药瓶进行台式实验。这些研究将 证明该技术能够选择性地将氧气定量到瓶头中的0.01%水平 其检测极限优于常规基于激光HSA所实现的检测极限。的 实验研究还将证明，在不使用 主动氮气吹扫。从第一阶段研究中获得的知识将指导 在第二阶段计划期间制造的可现场使用的原型设计。在第一阶段计划中，PSI将 与一家生产和销售小瓶检测仪器的公司建立合作。的 工业合作者将为第二阶段制造的原型系统的现场测试提供场所 程序.