What is gamma irradiation?
Gamma irradiation provides a number of benefits in cost and sterility assurance. It can be applied under safe, well-defined and controlled operating parameters, and is not a heat- or moisturegenerating process. Consequently, there is no heat stress and condensate drainage or outgassing are not required. Most importantly, there is no residual radioactivity after irradiation.Beyond having a different lethality mode, characterising the radiation sensitivity of the product bioburden is another key difference from moist heat (steam) sterilisation. Radiationresistant biological indicators are not used. After the mean bioburden is quantified and sensitivity to a low radiation dose (~8-10 kGy) is established, a statistically determined higher dose (typically >25 kGy) can be applied to provide the appropriate sterility assurance safety margin for every unit in the batch. This safety margin is similar to that of moist heat sterilisation, where a target of <10–6 probability of a non-sterile unit (Sterility Assurance Level, SAL) is established.
A third difference is that the gamma dosage can be measured in each batch using detectors called dosimeters, which enable parametric release. Product batches subjected to gamma radiation do not need to be lotsample sterility tested for release.
Standards for validation of gamma sterilisation
Validation procedures for the sterilisation of single-use systems via gamma irradiation are well established and based on widely used industry standards. These standards are recognised by regulatory agencies globally in lieu of any specific regulatory guidance.
The international standards are harmonised among three official standards bodies: the American National Standards Institute (ANSI), the American Association of Medical Instrumentation (AAMI) and the International Standards Organization (ISO). Their common document is ANSI/AAMI/ISO 11137, Sterilization of Health Care Products — Radiation (1).
ANSI/AAMI/ISO 11137 comprises three parts: Part 1 covers requirements for development, validation and routine control of a sterilization process, Part 2 covers establishing the sterilization dose, and Part 3 provides guidance on dosimetric aspects, the measurement of the radiation dose. Part 2 describes 3 methods for establishing a sterilizing dose (with SAL <10-6). Methods 1 and 2 were designed with small medical devices in mind and involve determination of bioburden and multiple dose analyses that require over 100 or 200 units respectively, both for initial validation and for quarterly dose lethality audits. When we consider large single-use systems, which are made in relatively small batches, both of these methods can be very costly and time consuming. However, the standard provides a third method called VDmax (VD stands for verification dose). Rather than determining the minimum dose to achieve a SAL of <10–6, the VDmax Method substantiates the suitability of a predetermined dosage level, specifically 25 kGy or, for plastic devices with lower gamma tolerance, 15 kGy.
In conjunction with the publication of the VDmax method for doses of 25 or 15 kGy, additional doses were qualified and published by AAMI in their Technical Information Report 33:2005 (2). This is considered a supplement to ANSI/AAMI/ISO 11137 and they will likely be merged at the next scheduled revision. It expands the VDmax method to seven additional dosages; 17.5, 20, 22.5, 27.5, 30, 32.5 or 35 kGy, enabling flexibility of minimum sterilising dosage based on mean bioburden levels for the product.