Larry NicholsBob StarrettOrdinarily, changing from a validated gamma sterilization process to E-beam sterilization requires running a dose mapping study and doing a dose verification study similar to a routine quarterly dose audit.

The standard radiation validation requirements of ISO 11137 require that data be “available to show that, using the same sterilization dose, microbial inactivation is not affected by differences between the two facilities in source characteristics, particularly radiation energy and the rate at which dose is delivered, or by differences in dose distribution throughout the product.”

Practically, this means that a dose mapping study must be performed at the new facility to conform the original validated sterilization dose can be adequately delivered by the E-beam throughout the product. Such a study is required when changing between gamma facilities too. It is especially important when changing to E-beam because some dense products or those in large packages may not be suited for E-beam sterilization even if they can be successfully sterilized by gamma irradiation. If a product is dense or the shipping cartons are large, modification of the outer package may make the e-beam process acceptable.

Secondly, a dose verification study must be done with the initial changeover lots. Most often, for routinely manufactured product that has a consistent bioburden history, running a routine quarterly dose check with the initial lot will confirm that microbial inactivation is similar between gamma and E-beam. For a new product, or if a consistent bioburden level has not been otherwise established, we recommend the bioburden be estimated using three current lots of product and the verification dose study be carried out just as if you were initially validating the process.

If the manufacturer is producing small or infrequent production batches and is using AAMI TIR27:2001 as the validation method, the dose verification study needed for the gamma/E-beam changeover is accomplished by running the routine quarterly verification experiment required by that standard.

The manufacturer should allow enough time for the dose mapping and dose verification to be complete before product using the process must be released for use. Lack of initial validation of sterilization or not validating changes to the process before release of a product is a major issue with both FDA and the European Community. If the products are subject to review by a registrar/notified body for compliance with the medical device directive, the manufacturer should check with his registrar to determine if this changeover requires contacting the notified body. If the product is a PMA device, a 180 day letter must be submitted to the FDA. For most products, if data is collected in compliance with the standards as above and the new facility is certified to ISO 13488 or ISO 13485 and EN552 by a notified body, the matter will be handled retrospectively in surveillance audits.

It is usually recommended that biocompatibility and safety tests be rerun using the new sterilization process.

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