Compact Hydrogen Peroxide Sensor for Sterilization Cycle Monitoring

描述（由申请人提供）：生产设施灭菌不当或不完全是药品召回的主要原因。这些召回的经济和社会影响是重大的，难以量化。许多制药公司使用气相过氧化氢（VPHP）来净化和消毒生产设施，包括屏障隔离器。一个可靠的仪器，具有大的动态范围和高灵敏度，用于监测VPHP在屏障隔离器去污将是非常宝贵的制造商，以提高产品的无菌保证和质量。物理科学公司(PSI)建议开发一种商业原型传感器，该传感器将促进快速可靠地开发去污循环、设备鉴定和屏障隔离器的连续监测，从而显著改善无菌保证、药物质量和可用性。该仪器将使用可调谐二极管激光吸收光谱法（TDLAS）测量VPHP和水蒸气，该光谱法具有新颖的量子级联激光器和腔增强光谱法。VPHP是一种常用的去污剂，必须仔细监测以确保无菌保证，并且由于其对药品的有害影响，必须在药品灌装操作之前将其去除至非常低的水平。该传感器将用于研究隔离器内的气相去污剂流量以及过氧化氢破坏、吸附和解吸对通常用于制造隔离器和药品灌装/成品包装操作的材料的影响。这个小型企业创新研究第一阶段/第二阶段项目解决了对药品灌装和包装系统中微量VPHP实时测量的迫切需求。屏障隔离器越来越多地用于新生物药品的生产和包装。该工具将能够建立一个关键的信息数据库，供制药业使用。具体的项目创新是使用新的量子级联激光技术和腔增强光谱技术，以实现整个周期中关键去污参数的超灵敏检测，并允许调查真实世界的灌装/成品参数（例如包装材料对VPHP的吸收）。该传感器的其他应用包括冻干机的去污监测和VPHP对医院病房中耐甲氧西林金黄色葡萄球菌（MRSA）污染的破坏。没有市售的传感器可以在生产规模操作的整个净化和净化循环中提供连续的VPHP测量。拟议的传感器将提供这种能力，允许实时过程监测和控制。这项开发针对USFDA过程分析技术（PAT）计划，旨在提高药品质量，增加疫苗等关键药品的可用性，并降低处方药产品的成本。

DESCRIPTION (provided by applicant): Improper or incomplete sterilization of manufacturing facilities is a major cause of pharmaceutical product recalls. The economic and societal impact of these recalls is significant and difficult to quantify. Many pharmaceutical companies use vapor phase hydrogen peroxide (VPHP) to decontaminate and sterilize production facilities, including barrier isolators. A reliable instrument with a large dynamic range and high sensitivity for monitoring VPHP during barrier isolator decontamination would be invaluable to manufacturers to improve product sterility assurance and quality. Physical Sciences Inc. (PSI) proposes to develop a commercial prototype sensor that will facilitate rapid and reliable development of decontamination cycles, equipment qualification and continuous monitoring of barrier isolators, enabling significant improvements to sterility assurance, drug quality and availability. The instrument will measure VPHP and water vapor using tunable diode laser absorption spectroscopy (TDLAS) with novel quantum cascade lasers and cavity enhanced spectroscopy. VPHP is a commonly used decontamination agent which must be carefully monitored to ensure sterility assurance and must be removed to very low levels prior to pharmaceutical filling operations due to its deleterious effects on pharmaceutical products. The sensor will be used to study vapor phase decontamination agent flow within an isolator and the effects of hydrogen peroxide destruction, adsorption and desorption for materials commonly used to fabricate isolators and in pharmaceutical fill/finish packaging operations. This Small Business Innovation Research Phase I / Phase II project addresses an immediate need for real-time measurement of trace amounts of VPHP in pharmaceutical filling and packaging systems. Barrier isolators are finding increasing use in the production and packaging of new biologic drug products. The instrument will enable production of a critical database of information for use in the pharmaceutical industry. The specific program innovation is the use of new quantum cascade laser technology with cavity enhanced spectroscopy to enable ultra-sensitive detection of critical decontamination parameters throughout the cycle and allow investigation of real-world fill/finish parameters (such as packaging material uptake of VPHP). Additional applications of the sensor include decontamination monitoring of lyophilizers and VPHP destruction of Meticillin-Resistant Staphylococcus Aureus (MRSA) contamination in hospital wards. No commercially available sensor can provide continuous VPHP measurements throughout the entire decontamination and purge cycles in manufacturing scale operations. The proposed sensor will provide this capability, allowing real-time process monitoring and control. This development targets the USFDA process analytical technology (PAT) initiative for building quality into pharmaceutical products, increasing the availability of critical drug products like vaccines and reducing the costs of prescription drug products.