RT Journal Article
SR Electronic
T1 Nitrogen Dioxide sterilization follows log-linear microbial inactivation kinetics using Geobacillus stearothermophilus biological indicators
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2024.012997
DO 10.5731/pdajpst.2024.012997
A1 Richards, Thomas P
A1 Lisco, Delaney
A1 Bianchi, Tiffany
A1 Shahine, Gabriele
A1 Nyugen, Huyen
A1 Simmons, Natalie
A1 Dufresne, Sylvie
A1 Opie, David
YR 2025
UL http://journal.pda.org/content/early/2025/06/16/pdajpst.2024.012997.abstract
AB Aim: The primary purpose of this study was to determine the inactivation kinetics of Geobacillus stearothermophilus biological indicators (BIs) exposed to Nitrogen Dioxide (NO2) gas in the presence of humidity. Methods: BIs inoculated with 6 log10 G. stearothermophilus spores were used as a test substrate. Three BI Lots manufactured from each of three different BI spore crops were evaluated. Test cycles were run at room temperature with 80% relative humidity. Direct Enumeration methods were used to quantify the resistance of spores with surviving populations greater than 2 log10. Fraction Negative methods were used to calculate spore populations in the quantal region. The methods were combined in order to show spore inactivation from 6 log10 to approximately -2 log10. The D-Value and least-squares regression (R2) were calculated. Results: Over 100 Direct Enumeration and Fraction Negative Cycles were completed at a fixed NO2 concentration varying only time. Critical process parameters were maintained over all cycles. Empirical data confirmed a log-linear relationship over an 8 log10 population range with R2 values greater than 0.8, allowing for extrapolation of the curve to -6 log10. Study outcomes were comparable for all manufactured BI Lots. Conclusions: NO2 sterilization follows first-order log-linear microbial inactivation kinetics, which is consistent with a mechanism of action based on a single active species. Significance and impact of Study: This is the first study to report on the microbial inactivation kinetics of NO2 sterilization. Further, this is one of the few studies to demonstrate inactivation kinetics applying ISO methodology.