Ultra-sensitive Vapor Phase Hydrogen Peroxide Sensor for Decontaminating Pharmaceutical Manufacturing Facilities

用于净化制药生产设施的超灵敏气相过氧化氢传感器

基本信息

批准号：
10383016
负责人：
Brian E Brumfield
金额：
$ 92.85万
依托单位：
PHYSICAL SCIENCES, INC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10383016
关键词：
Automation Biological Biological Assay Biological Products Biological Response Modifier Therapy Calibration Cell Therapy Cells Chemistry Computer software Decontamination Detection Development Drug Costs Drug Industry Elements Engineering Ensure Environment Equipment Evaluation Freeze Drying Goals Government Head Start Program Hydrogen Peroxide Immune Impairment Laboratories Laboratory Study Lasers Manufacturer Name Measurement Measures Monitor Optics Oxides Persons Pharmaceutical Preparations Pharmacologic Substance Phase Process Research Residual state Signal Transduction Spectrum Analysis Sterilization System Techniques Technology Testing Therapeutic Training Vacuum Validation Water Work absorption base commercialization design detection limit drug production experience experimental study field study finesse innovation instrument instrumentation manufacturing facility medical specialties operation optical sensor oxidation physical science portability programs prototype real time monitoring research and development sensor sensor technology vapor water vapor

项目摘要

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.

项目概要/摘要 Physical Sciences Inc. (PSI) 正在开发一种传感器，可精确测量 ppbv 至约 1000 ppmv 该传感器将用于在线监测气相过氧化氢 (VPHP) 的浓度。用于注射药物填充/完成操作的屏障隔离器的 VPHP 浓度。准确、灵敏地监测 VPHP 至关重要，因为残留浓度低至 30 ppbv 已被证明会氧化生物制剂并降低其功效。灭菌对于最大限度地减少其对生物药品的有害影响至关重要，并可能导致高需求生物药品的短缺此外，VPHP 污染导致批次损失。导致药物成本增加和收入减少。基于可调谐激光吸收的光学传感器。现有光谱学 (TLAS) 可以监测 VPHP 浓度，检测限在 ppbv 范围内，然而，TLAS 方法容易受到高浓度水蒸气的干扰比曝气阶段的 VPHP 浓度大几个数量级这会损害现有基于光学的商业仪器的准确性，以及使得精确量化 ppbv 水平的 VPHP 变得具有挑战性。此外，传感器的鲁棒性不强。制造规模的操作，需要训练有素的用户和频繁的重新校准。计划中，PSI 展示了一种创新的传感方法，能够量化 38 ppbv 存在 20,000 ppmv 水的情况下的 VPHP 该方法具有从 ppbv 到 100% 的广泛动态范围。 1000 ppmv – 远高于当前的商用传感器，可监测 VPHP 浓度在第二阶段计划中，使用一台便携式仪器完成整个灭菌周期。基于台式实验的原型传感器将在实验室和实验室中制造和测试屏障隔离器和真空冷冻干燥机的现场测试将在一家公司进行。为制药行业建造屏障隔离器实验室研究将证明对 60 秒平均内≤ 10 ppbv，并且能够测量高达 ~1000 ppmv 的 VPHP 软件。将开发用于自动控制传感器，实现无人值守操作——这是该技术的商业化之路将是无人值守的操作。项目结束时在现场测试中得到了证明。