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

项目摘要/摘要 物理科学公司(PSI)建议开发一种基于激光的超灵敏传感器，以准确地 监测以下气相过氧化氢(VHP)的ppbv至~1000 ppmv浓度 非肠外药物制造设施的净化，生物和细胞疗法必须 在无菌条件下包装。准确和灵敏地监控VHP的能力是至关重要的， 低至30ppbv的残留浓度已被证明可以氧化生物制品并降低其 功效。需要在灭菌后准确监测VHP，以将其有害影响降至最低 对生物药品产品的影响，并可能造成高需求生物药品的短缺。在……里面 此外，VHP污染造成的批次损失导致更高的药品成本和收入减少。光学 基于可调谐激光吸收光谱(Tlas)的传感器可以监测vhp浓度。 然而，由于检测极限在ppbv范围内，tlas方法容易受到水的干扰。 浓度比VHP浓度大几个数量级的蒸汽 在净化的曝气阶段。这损害了现有的基于光学的 商业化的仪器仪表，使得精确量化ppbv级别的VHP具有挑战性。在……里面 此外，传感器不适用于制造规模操作，需要训练有素的用户和 频繁地重新校准。在第一阶段计划中，PSI建议展示一种创新的光学传感 一种量化VHP的方法，可抑制水的干扰，并可实现准确的量化 即使在10,000 ppmv的水存在的情况下，VHP的ppbv水平也是如此。这种方法还将有一个 比现有商用传感器更宽的动态范围，支持对VHP的监控 在整个消毒过程中。将开发一种详细的光谱模型，可用于 分析在台式实验期间收集的数据。将进行实验研究，以 演示光学方法的测量能力，可测量ppbv到~1000 ppmv 在10,000 ppmv的水存在下的VHP浓度-模拟实际情况 一家制药厂的去污工艺。光谱模型的精确度 为量化VHP而开发的将通过对气体进行同步测量来确认 样品带有校准的电化学传感器，可以测量VHP的ppmv水平。这些信息 从实验研究中获得，光谱模型将使可现场第二阶段的设计成为可能 原型系统将能够在300秒内测量VHP的ppbv水平 存在10000ppmv的水本底。 拟议的努力得到了一家全球知名的大型工业设备供应商的支持。 制药公司。

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.