Pharmaceutical Regulatory Affairs: Open Access

Inactivation of Endotoxin and Lipid A by Nitrogen Gas Plasma Exposure Running title: Inactivation Endotoxin and lipid A

Abstract

Hideharu Shintani

The gases plasma from several different gases has shown a sporicidal activity. From these gases, nitrogen gas was most difficult to produce atomic nitrogen radicals. However, these radicals have a high energy, indicating that nitrogen gas plasma could be used to sterilize microorganisms and inactivate endotoxins and lipid A. The sterilization mechanism of nitrogen gas plasma may be the synergistic effect of free radicals such as (OH radical and NO radical) and metastables (N2 or O2 metastable). Thus, the target microorganisms such as bioburden were damaged by degradation, which resulted in death. The biological indicator BI used in this study was Geobacillus stearothermophilus ATCC 7953 at an initial population of 106 CFU/carrier. Sterility assurance level (SAL) of 10-6 was confirmed by using the BI. In addition endotoxins were successfully inactivated by nitrogen gas plasma expossure. More than 5 log reduction of endotoxins could be attained within 30 minutes of nitrogen gas plasma exposure. Lipid A degradation by nitrogen gas plasma exposure was confirmed by LC-MS-MS. Material/functional compatibility was also maintained by nitrogen gas plasma exposure due to shallower penetration depth of 10-20 nm. No deterioration of polymers could be observed by nitrogen gas plasma exposure. Residual gases, if any, are non-toxic. From the above description, it can be said that nitrogen gas plasma sterilization is an alternative future sterilization method.