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.

Public Health Relevance

The proposed R&D effort will result in sensor for vapor phase hydrogen peroxide that will be capable of monitoring residual VHP after sterilization before finish/fill operations at parenteral drug manufacturer facilities. This will enable pharmaceutical manufacturers to minimize the loss or reduction in efficacy of biologic and cellular therapy pharmaceuticals due to oxidation from residual VHP. The capability offered by this sensor will help to reduce shortages of high demand biologics and cellular therapeutics.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1)
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Krepkiy, Dmitriy
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Physical Sciences, Inc
United States
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