Packaging ethylene oxide sterilization

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. 

The significance of this model is that it describes the optimal situation for water permeation into the spore and therefore ethylene oxide permeation to its target site as a function of the moisture content of the spore and the relative humidity of the environment during exposure. The rate of microbial inactivation therefore increases (as long as all other factors are held constant) with increased relative humidity during exposure. Kaye and Phillips [4] demonstrated a 33% RH optimum for microbial inactivation as a result of exposure to ethylene oxide. In practical situations it is better to err on the side of too much rather than too little moisture. With industrial-scale ethylene oxide sterilization, humidity levels are usually in the range of 50% to 60% RH. The upper limit is usually dictated by deleterious effects on packaging. 

Sterilization by exposure to ethylene oxide is bounded by at least four variables gas concemratton, time of exposure, temperature, and humidity. It is also affected by product design, packaging design, and the composition of packaging materials. The shape, size, and materials of construction of individual sterilizers, the location of gas entry ports, and the presence or absence of forced circulation may all influence sterility assurance. There is no theory to describe these interactions. Validation and routine control of ethylene oxide sterilization processes boils down finally to the integration of all of these variables by reference to biological monitors. 

Before validation even, very serious consideration must be given to the nature of the product that is intended to be sterilized and the type of packaging it is to be presented in. Again, it is only experience and experiment that can indicate and confimi the suitability of particular presentations for ethylene oxide sterilization. 

For air ingress at the end of the cycle, ethylene oxide sterilizers should be equipped with sterilizing fillers. Although the primary packaging material ought to have been chosen to be a barrier to microbial ingress, there remains the possibility that the significant pressure differentials and air How rates that are obtained at the end of sterilization may be beyond validated tolerances. 

The condition of the gas vaporizer is a further important consideraikMi to ethylene oxide sterilization. All cylinder supplies of ethylene oxide present the gas in liquid form under pressure, which must then be vaporized before admission to the sterilizer. Inadequate temperatures in vaporizers may lead to the introduction of liquid ethylene oxide into the sterilizer. This is undesirable because it will not fulfill its purpose and because of staining and damage to product and packaging. Overly high temperatures may lead to degradation of the ethylene oxide with resultant polymer buildup restricting gas flow in the feed lines. 

DURASUL components for hip and knee arthroplasty with packaging (Centerpulse Orthopedics, formerly Sulzer Orthopedics). (A) 28-mm and 38-mm diameter DURASUL acetabular liners. (B) DURASUL patellar component with packaging used for ethylene oxide sterilization. 

Because of the health and environmental issues with ethylene oxide sterilization, numerous manufacturers of medical products prefer sterilization by radiation. This method is clean, leaves no residue, and enables sterilization of packaged parts. Due to the complex safety technology and high capital investment, sterilization and shipping are often outsourced to specialized companies. 

Formaldehyde gas for use in sterilization is produced by heating formalin (37% wA aqueous solution of formaldehyde) to a temperature of 70-75°C with steam, leading to the proeess known as LTSF. Formaldehyde has a similar toxicity to ethylene oxide and although absorption to materials appears to be lower similar desorption routines are leeommended. A major disadvantage of formaldehyde is low penetrating power and this limits the packaging materials that eanbe employed to principally paper and eotton fabrie. 

Ethylene oxide and hydrogen peroxide are the typical gases for gas sterilization. Their advantage is that they can be used at much lower temperatures than steam sterilization 27-60 °C for ethylene oxide and 25-40 °C for hydrogen peroxide. Another advantage is that they do not cause damage to the product or the packaging. 

Flexible medical packaging is well suited to SBC for use in form, fill and seal machines. SBC have excellent formability, which allows for nearly perfect replication and filling of molds. To make a peelable seal, the SBC would need to be co-extruded with a lower melting substrate to act as the adhesive layer. The SBC structure provides good web formability and good toughness. It then has the versatility to be sterilized by 7-radiation, ethylene oxide or electron beam. 

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