Ultra-Sensitive Vapor Phase Hydrogen Peroxide Sensor for Decontaminating Pharmaceutical Manufacturing Facilities and Equipment

用于净化制药生产设施和设备的超灵敏气相过氧化氢传感器

• 批准号: 9907596
• 负责人: Brian E Brumfield
• 金额: $ 23.13万
• 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 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907596
• 关键词: Biological; Biological Response Modifier Therapy; Calibration; Cell Therapy; Cells; Custom; Data; Decontamination; Detection; Development; Drug Costs; Ensure; Environment; Equipment; Gases; Goals; Hydrogen Peroxide; Immune; Impairment; Industry; Knowledge; Lasers; Manufacturer Name; Measurement; Measures; Modeling; Monitor; Optics; Output; Oxides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Process; Research; Residual state; Residual volume; Sampling; Signal Transduction; Spectrum Analysis; Sterilization; System; Techniques; Test Result; Testing; Therapeutic; Time; Training; Water; Work; absorption; base; design; design and construction; drug production; experience; experimental study; finesse; innovation; instrument; instrumentation; manufacturing facility; operation; optical sensor; oxidation; physical science; programs; prototype; purge; quantum; ratiometric; research and development; sensor; vapor; water vapor

Project Summary/Abstract Physical Sciences Inc. (PSI) proposes to develop an ultrasensitive laser-based sensor to accurately monitor ppbv to ~1000 ppmv concentrations of vapor phase hydrogen peroxide (VHP) following decontamination of parenteral drug manufacturing facilities where biologic and cellular therapeutics must be packaged under aseptic conditions. The capability to accurately and sensitively monitor VHP 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 VHP 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 VHP contamination results in higher drug costs and reduced revenue. Optical sensors based on tunable laser absorption spectroscopy (TLAS) exist that can monitor VHP 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 VHP concentrations during the aeration phase of decontamination. This impairs the accuracy of existing optical-based commercial instrumentation, and makes it challenging to accurately quantify VHP 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 proposes to demonstrate an innovative optical sensing approach to quantify VHP that suppresses interference from water, and will enable accurate quantification of ppbv levels of VHP even in the presence of >10,000 ppmv water. This approach will also have a broader dynamic range than existing commercial sensors can achieve, enabling monitoring of the VHP throughout the entire sterilization cycle. A detailed spectral model will be developed that can be used to analyze the data collected during the benchtop experiment. Experimental studies will be executed that will demonstrate the measurement capability of the optical approach to measure ppbv to ~1000 ppmv concentrations of VHP in the presence of >10,000 ppmv of water – conditions emulating the actual decontamination process at a pharmaceutical manufacturing facility. The accuracy of the spectral model developed to quantify the VHP will be confirmed by carrying out simultaneous measurements of the gas sample with a calibrated electrochemical sensor that can measure ppmv levels of VHP. The information gained from the experimental studies and the spectral model will enable the design of a fieldable Phase II prototype system that will be capable of measuring ppbv levels of VHP within 300 seconds of averaging in the presence of a water background that is >10,000 ppmv. The proposed effort has support of a well-known, worldwide industry equipment supplier for large pharmaceutical companies.

项目概要/摘要 物理科学公司 (PSI) 提议开发一种基于激光的超灵敏传感器，以准确 监测 ppbv 至 ~1000 ppmv 气相过氧化氢 (VHP) 浓度，如下 对生物和细胞疗法必须进行的肠外药物生产设施进行净化 在无菌条件下进行包装的能力至关重要，能够准确、灵敏地监测 VHP。 低至 30 ppbv 的残留浓度已被证明可以氧化生物制剂并降低其活性 灭菌后准确监测 VHP 对于最大限度地减少其有害影响至关重要。 生物药品，并可能导致高需求生物药品的短缺。 此外，VHP 污染造成的批次损失会导致药品成本增加和收入减少。 基于可调谐激光吸收光谱 (TLAS) 的传感器可以监测 VHP 浓度 检测限在 ppbv 范围内，但 TLAS 方法容易受到水的干扰 蒸气的浓度比 VHP 浓度大几个数量级 在净化的通气阶段，这会损害现有基于光学的精度。 商业仪器，并且使得精确量化 ppbv 水平的 VHP 变得具有挑战性。 此外，传感器对于制造规模操作来说并不稳健，需要训练有素的用户和 在第一阶段计划中，PSI 提议展示一种创新的光学传感技术。 量化 VHP 的方法可抑制水的干扰，并可实现准确的量化 即使存在 >10,000 ppmv 的水，这种方法也会产生 ppbv 水平的 VHP。 比现有商用传感器更宽的动态范围，从而能够监控 VHP 将开发一个详细的光谱模型，可用于整个灭菌周期。 分析在台式实验期间收集的数据将进行实验研究。 展示光学方法测量 ppbv 至 ~1000 ppmv 的测量能力 存在 >10,000 ppmv 水时 VHP 浓度 – 模拟实际情况的条件 制药厂的净化过程。光谱模型的准确性。 为量化 VHP 而开发的方法将通过同时测量气体来确认 带有校准电化学传感器的样品，可以测量 VHP 的 ppmv 水平。 从实验研究中获得的结果和光谱模型将有助于设计可部署的第二阶段 原型系统将能够在平均 300 秒内测量 VHP 的 ppbv 水平 存在 >10,000 ppmv 的水背景。 拟议的工作得到了一家知名的全球工业设备供应商的支持，用于大型 制药公司。