Using nitric oxide (NO) for gas sterilization at room temperature: A novel sterilization modality.

Abstract

The success of terminal sterilization is a critical step for medical device manufacturing to guarantee device functionality and limit infections. The Food and Drug Administration (FDA) Established Category A approved sterilization methods include heat (steam or dry), radiation (gamma, X-ray, electron beam), ethylene oxide (EtO) gas, and vaporized hydrogen peroxide (VH2O2). Although EtO is the most commonly used method in the industry, its high toxicity has always been a major concern for human health, environmental impact, and medical device integrity. The developement of novel alternative technologies are actively encouraged by the FDA, aiming to provide similar scalable sterility assurance level (SAL) as EtO gas while reducing health and environmental issues. Nitric oxide (NO) gas was evaluated as the novel sterilant provided by Sterile State Inc. (Grand Rapids, MI) to achieve SAL of 10-6 at room temperature (RT) and regular atmospheric conditions (21% oxygen and ambient pressure). Commercially available biological indicators (BIs) designed for heat, EtO, and VH2O2, and widely used spore species, including B. atrophaeus, B. subtilis and G. stearothermophilus, were used to validate the NO sterilization system. All the species showed a Log-linear reduction pattern under NO sterilization according to ISO 11138-1 guidelines, and the D-values of these microorganisms were determined. NO's ability to inactivate clinically relevant bacteria, E. coli and S. aureus, was also evaluated through D-values. The sterilization cycle was performed at RT, specifically at 21-23 °C, regular atmospheric pressure, and the NO dose potentially exposed to end-users was significantly less than National Institute for Occupational Safety and Health (NIOSH) defined human Immediately Dangerous to Life or Health (IDLH) level. For the first time, we proved the utility and effectiveness of NO as an agent to achieve sterilization at mild conditions using BI and the SAL of 10-6 standard. NO sterilization holds great potential to be used as a green alternative to traditional gaseous sterilant sterilization for medical device manufacturing and infection control.