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