Page 37 - Assurance of Sterility for Sensitive Combination Products and Materials

Terminal sterilization 25

Thus, product release after radiation terminal sterilization processing relies
neither on a test for sterility [21] nor on the assay of a biological indicator
(BI) [22] for product release. Product approval is based on parametric release
(dosimetric release); a declaration that the product is sterile based on records
demonstrating that the process parameters (absorbed dose) were delivered
within the specified range [23].

3.1.2 History of EO sterilization

EO was first isolated in 1859 by the French chemist Charles-Adolphe
Wurtz and by the early 20th century it was being used as a fumigant for
insects. In the late 1920s, Llyod A. Hall identified a vacuum process using
EO gas to sterilize spices used in packaged meats. This was shown to prevent
premature spoilage of meats caused by the bacteria in the seasoning spices.
The EO terminal sterilization process exposes product surfaces to gaseous
EO. It is a powerful alkylating agent that reacts and denatures nucleic acid
and proteins resulting in nonviable microorganisms. EO is a highly effective
surface sterilant but, because it does not penetrate, it requires gaseous contact
of all surfaces for it to be effective. Product and product packaging intended
to be EO sterilized must be permeable to heat, humidity, air, and EO [6].
The critical process parameters that impact lethality of EO are as follows:
(a) concentration of EO
(b) temperature of the product prior to and during exposure to EO
(c) pressure/vacuum conditions affecting product load uptake of EO a
(d) humidity in terms of steam impacting the product uptake of EO 1
(e) packaging and product that impact diffusion of EO to the surfaces
(f) time during which specified thresholds of parameters ‘a’ through ‘e’
occur
Unlike radiation sterilization, multiple process parameters must be con-
trolled and monitored throughout each phase of the EO sterilization pro-
cess. In addition to sterility, other critical factors typically evaluated in the
validation are residuals [24] and endotoxins [25]. The sterilization process
must also demonstrate EO, ethylene glycol (EG), and ethylene chlorohydrin
(EC) residuals as well as endotoxins must be proven to be below regulated
thresholds levels. Although the EO sterilization process is typically validated,
monitored, and product is released with BIs [22], parametric monitoring
and release can also be used [6].

a Note: pressure/vacuum/packaging/product does not directly affect the lethality. However,
it does affect the movement of EO and moisture into product load, thereby affecting the
efficacy of EO process lethality.