Gamma irradiation sterilization is performed by exposing product to a radiation source

Steam it? Gas it? Zap it? That may sound like the popular Hasbro kids toy “Bop It”, but can also refer to the “big three” of processes available for sterilizing disposable medical devices.

Selecting the right sterilization process for your application requires consideration at an early stage in development.

Characteristics like geometry, material composition, and construction all impact whether a particular sterilization technology will work for your product. For a disposable we worked on recently, the construction of the device included a variety of plastics, stainless steel, and adhesives to hold the components together; the geometry featured long, small diameter tubing that makes contact with a therapeutic agent.

When considering the available sterilization processes three main contenders present themselves: autoclaving, ethylene oxide (EtO) gas, and gamma irradiation. Autoclave sterilization – the use of pressurized steam to kill bacteria and other contaminants – requires high temperatures and was incompatible with the plastics and adhesives in the product. Ethylene Oxide Gas (EtO) was also eliminated due to the challenging geometry: gas is unlikely to adequately travel through the small diameter tubing in the device and kill the microorganisms present on its surface. This left an obvious choice: gamma irradiation.

Gamma irradiation sterilization is performed by exposing the product to a radiation source, typically Cobalt 60 isotope, which decomposes into Nickel 60 isotope, firing off gamma rays in the process. These gamma rays can penetrate through the entire product, deactivating whatever microorganisms may be present.

In order to take your product from early stage development to certified sterility, several steps are required. Below I present 5 tips for preparing your product for gamma irradiation sterilization in ongoing production:

1)      Engage early:
Get in touch with a sterilizer early: my experience is that they are happy to provide guidance, make recommendations, and help you design your product for irradiation. I also recommend attending a webinar and picking up a copy of ISO 11137: the gamma irradiation sterilization equivalent to IEC 60601. These resources will help you familiarize yourself with the terminology and the sterilization validation process.

2)      Establish your Max Dose:
Gamma radiation is applied as a dose that is measured in kilo-Gray (kGy), and each irradiation dose has a tolerance or range associated with it. For example, to ensure a sterilization dose of 35 kGy is achieved, the delivered radiation measured on the product may range from 35 to 45 kGy. However, if the product begins to disintegrate at or near 45 kGy, the delivered dose must be decreased potentially resulting in too low a dose to achieve sterility.
The product being irradiated must withstand a sufficiently high maximum dose that the minimum dose required to render the product sterile allows for a manageable range.  Generally, a maximum dose should target 45‑50 kGy or higher to ensure a suitable sterilization (or minimum) dose can be achieved. A lower maximum dose may be possible, but alternative and more expensive methods of setting the sterilization dose may be required later in the process.

3)      Lock down your design:
Product design, supply chain, and manufacturing process all impact whether a product can be repeatedly sterilized: something as simple as changing your raw material supplier may change the level of bioburden (the number of living microorganisms present on the product). If the bioburden changes, so too can the required sterilization dose, which means re-validation of the dose and more cost to you.

4)      Prepare a plan:
When pursuing regulatory approval to sell your device, regulatory bodies will undoubtedly take an interest in how you plan to process your product for sterility. For example, ahead of a FDA 510(k) submission, you must be able to describe the sterilization method that will be used – and in the case of gamma irradiation – the radiation dose; the method or plan for validating the sterilization cycle (the VDmax25 method is preferred due to the reduced statistical sample requirements); the sterility assurance level  (which is typically 10^-6 or a 1 in 1 million chance a product is non-sterile despite being irradiated); and a description of the packaging used to keep the product sterile.

5)      Execute:
It’s go-time! Your product’s design is complete, the materials are locked down, and the product is ramping up into production: you’re ready to sell… almost. The first off the line units (or pre-production units as they are called at StarFish) make excellent candidates for sterilization validation. The number of units required will vary depending on the size and complexity of the product and validation method selected. For the tubing based product, the team budgeted for 80-100 units to be consumed including the radiation dosing, analytical chemistry, and long term shelf life testing that make up a sterilization validation program.