Sterilization, ethylene oxide

Hospital sterilizer loads vary in composition, thus the challenge presented to the test organism can vary considerably, depending on the type and contents of packages in which they are placed. The benefits of a standardized test-pack constmction and test protocol are obvious, and such recommendation is made by AAMI for steam and ethylene oxide sterilizers (11). More recentiy in European (CEN) and International (ISO) standards, biological indicators are considered as additional information supplemental to the measurement of physical parameters. Indeed, for sterilization using moist heat (steam), the biological indicator information is not considered to be relevant. 

It is necessary to determine the bioburden and make cycle verification studies when ethylene oxide sterilization is used, as it is for other sterilization methods. The manufacturer of hospital sterilization equipment provides cycle recommendations based on the expected bioburden and the consideration of an appropriate safety factor. In ethylene oxide sterilization, it is necessary to determine if residues of the stefilant are absorbed by the sterilized article, and to examine the possible formation of other potentially toxic materials as a result of reaction with ethylene oxide. 

Organisms are more resistant to ethylene oxide treatment in a dried state, as are those protected from the gas by inclusion in crystalline or dried organic deposits. Thus, a further condition to be satisfied in ethylene oxide sterilization is attainment of a minimum level of moisture in the immediate product environment. This requires a sterilizer humidity of 30-70% and frequently a preconditioning of the load at relative humidities of greater than 50%. 

The operation of an ethylene oxide sterilizer should be monitored and controlled automatically. A typical operating cycle for pure ethylene oxide gas is given in Fig. 20.7, and general eonditions are summarized in section 10. 

Syringes (disposable) Gamma-radiation Ethylene oxide Sterilization Gamma-radiation Possibility of crazing of syringes after ethylene oxide... 

The sterilization processes described in the Ph Eur are preferred, especially terminal sterilization in the final container alternative processes have to be justified. All sterilization processes will need to be described and appropriate in-process controls and limits included. Where Ph Eur prescriptions are followed, there should be a statement to this effect in the application. Most of this information should be discussed in the development pharmaceutics section. Reference is made to the specific guidelines on ethylene oxide sterilization and irradiation sterilization, which are discussed further below. The possibility of parametric release for terminal processes such as saturated steam and irradiation is mentioned (see below). For all sterile products there should be a sterility requirement included in the finished product specification regardless of the outcome of validation studies. 

In the case of ethylene oxide sterilization, rather more detail is included on the information expected in an MAA description of the sterilizer and associated facilities, the gas concentration used, bioburden monitoring and limits prior to exposure to gas, gas exposure time, temperature and humidity prior to exposure and during the exposure cycle, and the conditions under which ethylene oxide desorption is undertaken. 

In addition to the general guidelines on sterilization issues, there are two specific guidelines on the use of ethylene oxide sterilization (3AQ3a, adopted in 1994)... 

It has been shown that new technological processes applied in food production, such as ethylene oxide sterilization, UV-C irradiation, or prolonged storage, may promote formation of new allergens (Sanchez-Monge et al., 1999). 

Ethylene oxide sterilized laonofilaments of copolymer II-A and a poly(p-dioxanone) were compared in terms of their in-vivo absorption and BSR (breaking strength retention) profiles. The BSR and absorption studies were conducted in rats according to the procedures described elsewhere. The comparative data of these studies are given in Table V. 

Robertson, J. H., Townsend, M. W., Allen, P. M., et al. Validation of ethylene oxide sterilization cycles. Bull Parenter Drug Assoc 3P.265-273 (1977). 

Halleck, F. E. Principles for the validation of ethylene oxide sterilization cycles. Med Dev Diag Ind 2 27 (1980). 

Caputo, R. A., Rohn, K. J., Macoli, C. C. Biological validation of an ethylene oxide sterilization process. Dev Indus Microbio 22 357-362 (1981). 

In step 5, the qualification stage, the critical issue is that the protocol for IQ/OQ of the equipment and the facility include the established method and acceptance criteria. The IQ/OQ report should include the maintenance program to keep the equipment in good condition for reproducibility of the product. For qualification of the equipment and process for terminal sterilization, the following standards should be referred to ISO 13408-1 [6] and 11138-1 [7] for general issues, ISO 11134 [8] and 11138-3 [9] for moist heat sterilization, ISO 11135 [10] and 11138-2 [11] for ethylene oxide sterilization, and ISO 11137 [12] for radiation sterilization. 

ISO 11135. Sterilization of Health Care Products—Requirements for Validation and Routine Control of Ethylene Oxide Sterilization. Switzerland (1998). 

Microfiltration cartridges produced for this market are often sterilized directly after manufacture and again just prior to use. Live steam, autoclaving at 120 °C, or ethylene oxide sterilization may be used, depending on the applications. A flow schematic of an ampoule-filling station (after material by Schleicher and Schuell) is shown in Figure 7.18. 

Burgess, D., Reich, R. Industrial ethylene oxide sterilization. In Morrissey, R., Phillips, G.B. (eds.). Sterilization Technology A Practical Guide for Manufacturers and Users of Health Care Products. New York Van Nostrand Reinhold, 1993. 

Comparing Figs. 28 and 29, accelerated aging affects the fatigue resistance of all UHMWPE samples. Again, gas-plasma and ethylene oxide sterilization as well as the nonsterilized product show little differences after aging,... 

Table 1. Manufacturers of Steam, Ethylene Oxide Sterilizers, and Dry Heat Sterilizers...

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