Ultra-Sensitive Vapor Phase Hydrogen Peroxide Sensor for Decontaminating Pharmaceutical Manufacturing Facilities (2nd Admin Supplement Request)

用于净化制药生产设施的超灵敏气相过氧化氢传感器（第二次管理补充请求）

• 批准号: 10885691
• 负责人: Brian E Brumfield
• 金额: $ 26.71万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10885691
• 关键词: Biological; Biological Products; Biological Response Modifier Therapy; Calibration; Cell Therapy; Computer software; Decontamination; Detection; Drug Costs; Drug Industry; Elements; Freezing; Hydrogen Peroxide; Impairment; Laboratories; Laboratory Study; Lasers; Manufacturer; Measures; Monitor; Optics; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Residual state; Spectrum Analysis; Sterilization; Technology; Testing; Training; Vacuum; Water; absorption; commercialization; detection limit; experimental study; field study; innovation; instrument; instrumentation; manufacture; manufacturing facility; operation; optical sensor; oxidation; physical science; portability; programs; prototype; research and development; sensor; vapor; water vapor

Project Summary/Abstract Physical Sciences Inc. (PSI) is developing a sensor that can accurately measure ppbv to ~1000 ppmv concentrations of vapor phase hydrogen peroxide (VPHP). This sensor will be used for inline monitoring of VPHP concentrations of barrier isolators used for fill/finish operations of parenteral drugs. The capability to accurately and sensitively monitor VPHP is critical, as residual concentrations as low as 30 ppbv have been shown to oxidize biologics and reduce their efficacy. The need to accurately monitor VPHP after sterilization is critical to minimize its deleterious effects on biological drug products and potentially cause shortages of high-demand biologic pharmaceuticals. In addition, batch losses due to VPHP contamination results in higher drug costs and reduced revenue. Optical sensors based on tunable laser absorption spectroscopy (TLAS) exist that can monitor VPHP concentrations with limits of detection in the ppbv range, however the TLAS approach is prone to interference from water vapor which is present at concentrations several orders of magnitude larger than the VPHP concentrations during the aeration phase of decontamination. This impairs the accuracy of existing optical-based commercial instrumentation, and makes it challenging to accurately quantify VPHP at ppbv levels. In addition, the sensors are not robust for manufacturing scale operations, requiring highly trained users and frequent recalibration. In the Phase I program, PSI demonstrated an innovative sensing approach that was capable of quantifying 38 ppbv of VPHP in the presence of 20,000 ppmv water. This approach has broad dynamic range from ppbv to 1000 ppmv – far greater than current commercial sensors, enabling monitoring of VPHP concentrations throughout the entire sterilization cycle with a single instrument. During the Phase II program, a portable prototype sensor based on the benchtop experiment will be fabricated and tested in the laboratory and in field testing on a barrier isolator and a vacuum freeze dryer. Field testing will occur at a company that builds barrier isolators for the pharmaceutical industry. Laboratory studies will demonstrate a detection of ≤ 10 ppbv in 60 seconds of averaging, and the capability to measure up to ~1000 ppmv of VPHP. Software will be developed to automate control of the sensor, enabling unattended operation – a critical element in the path towards commercialization of the technology. Unattended operation of the sensor will be demonstrated in field testing by the end of the program.

项目总结/摘要 物理科学公司(PSI)正在开发一种可以精确测量ppbv到~1000 ppmv的传感器 气相过氧化氢（VPHP）的浓度。该传感器将用于在线监测 用于胃肠外药物灌装/成品操作的屏障隔离器的VPHP浓度。的能力 准确和灵敏地监测VPHP是至关重要的，因为残留浓度低至30 ppbv 被证明会氧化生物制剂并降低其功效。需要准确地监控VPHP后， 灭菌对于将其对生物药品的有害影响降至最低是至关重要的， 高需求的生物药品短缺。此外，由于VPHP污染造成的批次损失 导致药物成本上升和收入减少。基于可调谐激光吸收的光学传感器 存在能够以ppbv范围内的检测极限监测VPHP浓度的TLAS， 然而，TLAS方法容易受到水蒸气的干扰，水蒸气的浓度 几个数量级大于VPHP浓度在曝气阶段， 净化这损害了现有的基于光学的商业仪器的准确性，并且 这使得在ppbv水平上准确量化VPHP具有挑战性。此外，传感器对于 制造规模的操作，需要训练有素的用户和频繁的重新校准。在I期 PSI展示了一种创新的传感方法，能够量化38 ppbv的 VPHP在20，000 ppmv水的存在下。这种方法具有从ppbv到 1000 ppmv -远高于目前的商业传感器，能够监测VPHP浓度 在整个灭菌周期中使用单个仪器。在第二阶段计划中， 基于实验台实验的原型传感器将在实验室和 在屏障隔离器和真空冷冻干燥机上进行现场测试。现场测试将在一家公司进行， 为制药行业制造屏障隔离器。实验室研究将证明检测到 在60秒的平均时间内≤ 10 ppbv，并且能够测量高达~1000 ppmv的VPHP。软件 将开发自动化控制的传感器，使无人值守的操作-一个关键因素， 走向技术商业化的道路。传感器的无人值守操作将 在项目结束时进行实地测试。