Pharmaceutical Regulatory Affairs: Open Access

Sterilization Validation of Gas Plasma Exposure Based on ISO Documents (Mainly ISO TC 198 And 194 Documents)

Abstract

Hideharu Shintani

There are so many ISO documents to understand and utilize for validation studies and routine control. A biological indicator (BI) is essential for conducting sterilization validation and routine control. ISO 11138-1 and ISO 14161 are the major documents to follow for BI manufacturers and BI users, respectively. In ISO 11138-1, BI manufacturers must utilize a BI with 10⁶ CFU/carrier as an initial population for validation studies. For routine control, it is approved to use an initial BI population of 10⁵ CFU/carrier according to ISO 11138-1. In ISO 14161 BI users need not imitate BI manufacturers and less than 10⁶ CFU/carrier BI is approved for use in validation studies and routine control. According to ISO 14161 for BI users, the initial population must be identical for validation studies and routine control. For the BI user, there are four types of procedures for sterilization validation and routine control. These are the half-cycle, over-kill, combined BI/bioburden and the absolute bioburden methods. A BI with An initial population of 10⁶ CFU/ carrier must be used for validation studies by BI manufacturers according to ISO 11138-1, but BI users can elect to use a commercially available BI with more than 103 CFU/carrier as the BI for validation studies and routine control as described in ISO 14161. The approved SAL was defined to be 10^-6 and this is unchanged for both BI users and BI manufacturers. Therefore, from the initial population of 10⁶ CFU (colony forming unit)/carrier to a SAL of 10^-6, the survivor curve must be straight and tailing is not allowed as described below (ISO 11138-1). The BI used for gas plasma sterilization, spores of Geobacillus stearothermophilus ATCC 7953, has characteristics that do not result in a tailing phenomenon. A linear survival curve is obtained from an initial population of 10⁶ CFU/carrier to a SAL 10^-6 for all sterilization procedures tested, demonstrating that inactivation kinetics are first order and allowing calculation of the D (decimal reduction) value from the dose or time to decrease 1 log. Chemical indicators (CI) are not approved for use in validation studies; only the use of BI is approved. CIs are only approved for use as a supporting method during routine control according to ISO 11140-1 and 14161. Only a BI is approved for both validation studies and routine control according to ISO 14161.