devices constitutes by far the largest enterprise among these activities. Sterigenics, Inc., estimates that the current medical device radiation sterilization market is approximately 5.7 million cubic meters per year (m3/yr, or 200 million cubic feet per year, ft3/yr), with about 80 percent using gamma irradiation and about 20 percent using e-beam irradiation (Smith, 2006). This is probably around half of the entire sterilization market, the rest being carried out using other methods. Whether irradiating flies, food, or syringes, these applications generally require high-throughput irradiation to be economically and/or logistically practical. To achieve high throughput, irradiator facilities use large numbers of high-activity radiation sources. As mentioned in Chapter 2, the activity in cobalt-60 sources in panoramic irradiators accounts for over 98 percent of the total activity in all civilian radiation sources in the United States.
The Food and Drug Administration (FDA) requires that the sterilization of invasive medical devices such as hypodermic needles and scalpels must achieve a sterility assurance level of 10−6.2 The sterility assurance level is the probability or frequency of contaminated products after processing, so a level of 10−6 corresponds to a one in a million chance that one live microbe is in the sterilized load. Three standard sterilization processes are employed worldwide by the majority of single-use medical device manufacturers: gamma irradiation, e-beam irradiation, and ethylene oxide (EO) gas diffusion. Some features of these sterilization methods are summarized in Table 6-1. Also shown in the table are features of autoclave (steam) or dry-heat sterilization, which is usually reserved for multiuse medical devices.
X-ray irradiation is not yet used in a major facility, but it is included with gamma irradiation because x-ray generators can meet or exceed the specifications for gamma irradiators listed in the table. The critical differences between these two types of irradiation are discussed in the section of this chapter on x-ray irradiators.
Because gamma radiation penetrates through a product, killing pathogens along its path, yet does not heat the packaging or the product significantly, it can be used to sterilize devices already sealed in heat-sensitive, air-tight plastic packaging. This is a significant benefit for some single-use medical devices and kits, such as those containing hypodermic needles preloaded with a pharmaceutical. Gamma irradiation has proven performance in killing pathogens and is one of the preferred methods, as evidenced by the quantity of product irradiated each year. To achieve a 10−6 sterility assurance level requires a dose in the range of 15 to 40 kGy (commonly 25 kGy) at the most shielded point in the package, per ISO Standard 11137.
A sterility assurance level of 10−3 is used for many noninvasive medical devices. The doses associated with this level are lower and “kinder” to materials, especially in new drug/device combination products. ISO validation methods (ISO 11137-1, -2, and -3, and VD Max) allow for differing doses and product sterility assurance level depending on bioburden and product use.