Validation of a Novel Medical Device Sterilization Modality Using Nitric Oxide (NO): Sterility Efficacy and Initial Material Compatibility

Background: Terminal sterilization is a regulatory requirement for most medical devices. However, conventional sterilization methods can compromise temperature-sensitive and biologically reactive components. This study evaluates the sterilization efficacy and preliminary material compatibility of a novel room-temperature sterilization modality using gaseous nitric oxide (NO). Methods: NO was delivered using standardized Sterile Solution® (Sterile State Inc., Grand Rapids, MI, USA). To characterize microbial inactivation kinetics, the decimal reduction time (D-value) of commercial biological indicators (BIs), Bacillus atrophaeus Apex® Discs, was determined in accordance with ISO 11138. BIs were exposed to NO at ambient temperature (18.9–22.0 °C). D-values were calculated using both the survivor curve method (Holcomb–Spearman–Karber) and the fraction-negative method (Stumbo–Murphy–Cochran). Material compatibility was evaluated across four primary medical device and packaging plastics, including polyethylene (PE), poly(ethylene terephthalate) (PET), polypropylene (PP), and polyvinyl chloride (PVC)), representing 70% of the industry market share. After exposure to NO sterilization cycles, mechanical and chemical properties were characterized using tensile testing (ASTM D882-18) and Fourier-transform infrared (FTIR) spectroscopy relative to unexposed controls. Results: The calculated D-values ranged from 1.31 (78.7 min) to 1.34 h (80.4 min) across both analytical methods, corresponding to an estimated 6-Log reduction in Bacillus atrophaeus BIs in approximately 8 h. Meanwhile, plastics exposed to the NO sterilization cycle showed no significant changes in mechanical or chemical properties. Conclusions: These findings demonstrate that NO sterilization achieves semi-Log-linear inactivation of a widely accepted BI and represents a promising alternative to conventional gaseous sterilization methods such as ethylene oxide (EtO). By achieving a reliable sterility assurance level under mild ambient conditions without adversely affecting the physicochemical properties of commonly used plastic materials, NO sterilization may offer a practical solution for thermosensitive and delicate medical devices.