Chlorine dioxide gas sterilization of cold-chain or temperature-sensitive devices.

Abstract

Cold-chain terminal sterilization is used for products that must be manufactured, stored, and maintained with a carefully controlled temperature range, such as temperature-sensitive drugs and vaccines in prefilled syringes or autoinjectors containing temperature-sensitive drugs. Chlorine dioxide (ClO2) is an ideal sterilant for cold-chain terminal sterilization because it forms a true gas at room temperatures (15°C/59°F - 25°C/77°F), with a reliable and consistent process, with excellent penetration, and does not require elevated temperatures. In the current study, we validated the efficacy of ClO2 on cold-stored prefilled syringes as well as tested ClO2-sterilized samples and non-sterilized controls for residual sterilant on the prefilled syringe samples and the ingress of sterilant into the prefilled syringe samples. Residual sterilant remaining on a load after sterilization could cause chemical exposure to patients and negatively affect healthcare worker safety, among other things. Sterilant ingress into a medication could result in chemical contamination, drug degradation, and changes to drug formulation. Few studies have been published on ClO2 residue or ingress during terminal sterilization. Through this descriptive analysis of residual and ingress testing results, we demonstrate that chlorine dioxide sterilization leaves chlorite and chloride residuals at acceptably low levels. The residual chlorite average was 0.74 mg/L (control) and 0.82 mg/L (sterilized), which are below the maximum contaminant acceptable level of 1.0 mg/L. We also demonstrated that there was no evidence of any ingress,and that the amounts remained at acceptably low levels: average ingress chlorite was 0.78 mg/L (control) and 0.72 mg/L (sterilized), below the maximum contaminant acceptable level of 1.0 mg/L. Chlorate has no known maximum contaminant level. ClO2 sterilization is an excellent alternative to ethylene oxide sterilization for cold-chain sterilization because it is sustainable, non-carcinogenic, and does not leave harmful residuals, nor does it ingress into the drug product. This study helps demonstrate that ClO2 is a viable primary or alternative sterilization modality for medical device manufacturers.