Packaging materials. The radiation stability of packaging and container materials must never be overlooked when considering radiation compatibility. Lists of radiation-compatible packaging materials are readily available (1, 6, 22–25).

Validation of radiation sterilization

Validation of the radiation-sterilization process is an integral aspect of good manufacturing practice. It comprises installation qualification (IQ), operational qualification (OQ), performance qualification (PQ), materials compatibility, selection of sterilization dose, and routine process control. These components of validation relate either to the irradiation facility itself or the product being irradiated.

The essential parameter that must be controlled in radiation sterilization is measurement of radiation dose. Measurement is achieved using dosimeters, which are chemical or physical systems that respond quantitatively to absorbed radiation doses.

OQ demonstrates that the installed irradiator can operate and deliver appropriate radiation doses within defined acceptance criteria. PQ is essentially dose mapping. During dose mapping, the location and magnitude of the minimum and maximum delivered doses must be identified.

Radiation units. The absorbed radiation dose generally is expressed in rads (radiation absorbed doses). One rad is equivalent to an absorbed energy of 100 erg/g of material. The currently used SI unit for radiation-absorbed doses, however, is the gray, which is equivalent to an energy absorption of 1 joule/kg. One gray is equivalent to 100 rad, and 25 kGy, a common radiation dose for sterilization, is equivalent to 2.5 Mrad.

Determination of sterilization dose

An integral part of sterilization-process validation is the determination of a radiation dose for sterilization. Any deviation from the selected dose could either compromise the sterility of the product or damage the product.

A radiation dose of 25 kGy (2.5 Mrad) generally is accepted as suitable for sterilization purposes. This dose was chosen according to the radiation resistance of the bacterial spores of Bacillus pumilus. Today, the choice of radiation dose is based on the presterilization microbial contamination, or bioburden, and the desired sterility assurance level (SAL) of the product. Such considerations are based in part on extensive studies of the effects of substerilization doses on different microbial populations (27, 28). SAL is defined as the probability of a single viable microorganism occurring on a product following sterilization. SAL normally is expressed as 10^–n. While the majority of authorities give n a value of 6, FDA does allow values of less than 6 for noninvasive products.

Most regulatory authorities expect radiation sterilization doses to be selected according to one of the methods of the International Organization for Standardization (ISO) standard, ISO 11137-2:2006 (Sterilization of Health Care Products—Radiation—Part 2: Establishing the Sterilization Dose). ISO 11137:2006 is published in three sections that discuss radiation sterilization, establishing the sterilization dose for radiation sterilization, and dosimetric aspects of radiation sterilization. The dose-setting methods described in the AAMI–ISO standards owe much to the ideas first presented by Tallentire and his colleagues (26).

The first ISO method, designated Method 1, is certainly the most common method used for dose selection for sterilization. The method requires the average microbial contamination of representative samples of the product to be determined. Note that the microbial population's radiation resistance is not determined. Dose setting is based on manufacturers' data about the resistance of microbial populations. The distribution of the chosen resistance is assumed to represent a more severe challenge than that presented by the natural bioburden of the article to be sterilized. The assumption is verified experimentally by irradiating 100 samples at a given verification dose and is accepted if no more than two contaminated samples remain. The sterilizing dose, which is appropriate for the average bioburden per sample and the desired SAL for the product, is then read from a table.