Gamma irradiation is a key technology for the sterilization and bioburden control of medical devices and single-use bioprocess systems. Gamma irradiation is a convenient means of sterilization since products to be sterilized may be bulk packaged and even palletized in some facilities, without special vapor permeable packaging required for ethylene oxide gas. Sterilization validation and parametric release is a relatively straightforward exercise outlined in ISO 11137, which can be conveniently applied to industrial processes allowing parametric release of lots based on bioburden assessments and dosimetry, without the need for sterility tests.
This blog offers valuable insights into gamma, E-beam and X-ray sterilization modalities as well as regulatory considerations. Learn about comparative studies by leading academic and trade organizations and the conclusions they draw on sterilization techniques.
The History of Gamma Irradiation
Since the early 2000s, there has been international pressure to move away from ethylene oxide as a sterilant for environmental considerations, with some facilities being shut down due to local real or perceived dangers to the surrounding community from emissions.
The International Atomic Energy Agency reports that more than 160 gamma irradiation facilities operating around the world, sterilize more than 40% of all single-use medical devices. Those same facilities are used to sterilize or reduce bioburden in nearly 100% of all single-use bioprocess systems used globally.
The source for gamma irradiation is Cobalt 60, a radioactive metal with a half-life of 5.3 years which must be produced in a nuclear reactor. Due to the relatively short half-life, the sources in these facilities must be replaced annually. The infrastructure and capacity to produce Cobalt 60 for the sterilization market has been fixed or in decline for many years, while the demand for irradiation capacity has steadily increased. From a safety and security perspective, significant global governmental pressures are being applied to reduce the dependency on Cobalt. New methods to irradiate are required to close the gap between expected demand and available supply. The available gamma irradiation capacity is predicted to become an issue within 1-3 years.
Gamma Irradiation Broken Down
Generically, gamma irradiation can be described as Ionizing radiation, with two viable replacement technologies. Electron beam (E-beam) irradiation is one potential replacement technology, however E-beam irradiation lacks the penetrating power of gamma, so it loses the convenience of being able to sterilize bulk packages. E-beam sterilization is therefore limited to surface sterilization or sterilization of small individual packages. X-ray as a source of ionizing radiation compares favorably to Cobalt 60 and E-beam and is now being promoted as the key technology to close the gap. X-ray facilities generate deep penetrating radiation that can deliver sterilization doses through large bulk packages. The facilities use technology that only emit radiation while the power is on. This makes the technology intrinsically safe, without dependency on nuclear reactors and source materials with inherent safety and security concerns.
From a microbiological point of view, the equivalence of gamma, E-beam and X-ray has been assessed with the conclusion that “dose is dose” and that a validated kill dose from any ionizing radiation source will provide equivalent kill at the equivalent dose.
Sterilization Studies on Medical Devices
Consideration of X-ray sterilization of medical devices has been performed by Team Nablo, a group of representatives from a national laboratory, academia, irradiation providers and a medical device company. Team Nablo set out to compare the effects of gamma irradiation, E-beam and X-ray on a representative medical device to establish equivalency based on functional tests, device discoloration and mechanical testing of select components. The intent of the study was to provide confidence to proceed with qualification of alternate sterilization techniques via similar scopes of study.
Single-use bioprocess systems are not regulated directly but are frequently used in drug manufacturing processes that must adhere to current good manufacturing processes governed in the United States by 21CFR211. 21CFR211.65 states that “Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.” This requirement changes the burden of proof required to qualify an alternative sterilization method.
The BioProcess Systems Alliance (BPSA), a trade organization representing the combined interests of single use bioprocess system manufacturers and end users has also been active in consideration of the transition to X-ray sterilization. The BPSA has published a white paper proposing a risk-based approach to qualify a material, component or single-use system for transition to X-ray from gamma. The risk-based approach increases the scope of study depending on the risk of the application of the component or system.
Listed below in risk-based order of increasing scope of study:
- Comparative material assessment via FTIR and DSC
- Comparative material assessment via physical / mechanical property tests (i.e. tensile tests)
- Comparative component or system functional testing
- Biological reactivity testing (USP Class <87>, <88> and ISO 10993-X
- Chemical testing (USP 661, extractables etc.)
The intent is to demonstrate equivalency of results to enable bioprocess end users to reduce the scope of study to demonstrate equivalency of the single-use system as it interacts within the end user’s process.
The transition to other modalities of sterilization is a foregone conclusion. The favorable aspects of X-ray suggest that it will be the modality of the future. Team Nablo and the BPSA have established roadmaps for suppliers to qualify alternate modalities to prepare for transition to X-ray.
Qosina, as a supplier to the medical device and bioprocess industries, has begun a project to qualify several materials and components for X-ray sterilization. As industry experts, we understand the strict regulatory considerations for gamma, E-beam and X-ray sterilization and remain committed to the needs of our customers for support for this transition. Subscribe to our Bioprocess newsletter to stay up-to-date on trends, insights and expertise in single-use systems.