This annex gives guidance only for the qualification of medical devices and is particularly relevant to medical devices fabricated from synthetic polymeric materials. For other health care products the effects of exposure to radiation on properties other than those outlined in this annex will need to be addressed. The indicators may be used to show that the products have been exposed to a radiation source. They should be used only to provide a qualitative indication of radiation exposure and may be used to distinguish process loads that have been irradiated from unirradiated process loads.

Prior to selecting the radiation sterilization process for a medical device, it is important to consider the effect that radiation will have on the stability of the materials that make up the devices or device components. While some materials such as polystyrene are inherently less affected by radiation than others such as polytetrafluoroethylene (PTFE) or polyoxymethylene, the radiation stability of any device will be a function both of the materials and the design (table A.1). Therefore, a programme to demonstrate functional stability of the device throughout its shelf life should be carried out.

Testing should include any specific property essential to the intended function of the device, such as strength, clarity, colour, biocompatibility and package integrity. The test programme should encompass all variations in manufacturing processes, tolerances radiation doses, radiation source, raw materials and storage conditions. Based upon the above considerations the maximum dose for each device shall be specified.

The effects of radiation dose on materials might not be immediately apparent. Therefore, the test programme may include accelerated ageing at extreme conditions for initial indication of material suitability, as well as ambient real-time ageing. The accelerated testing may include doses above those required simply to achieve sterilization, combined with storage at extreme environmental conditions. However, in most cases, ambient, real-time and non-irradiated control samples should be part of the test programme.

A typical testing protocol can require devices or material samples to be exposed to radiation at various dose levels between 10kGy and 100 kGy. The irradiation of test samples should be in accordance with C.1.5.4.

Although there is no substitute for long-term shelf stability studies, an accelerated ageing study can be used for screening of materials. In this case, the same test protocol for material testing is employed, but the temperature is held at 60oC. In the absence of a more accurate relationship, seven days at 60oC may be considered equivalent to 180 days of ageing at ambient conditions. A suggested time interval for accelerated testing is one week to 30 days. At ambient conditions, the suggested time intervals are 0, 3, 6, 9 and 12 months [2]. In all cases, non-irradiated material should be maintained as a control for the intended life of the device.

There are many tests employed in materials evaluation. Once a material is selected on the basis of these tests, final qualification to demonstrate functional stability of the device should be carried out on fully processed components, complete devices and packages, as appropriate. If testing of individual device components is done, a demonstration that the components are compatible with each other in a complete device should be part of the testing.

In addition to the physical and mechanical qualification testing some materials might need to undergo biocompatibility testing. Changes in the chemical structure of the polymer and/or its additives, as well as gaseous by products liberated during irradiation, can alter the material’s biocompatibility for medical device applications. This testing should also demonstrate biocompatibility throughout the intended life of the device ISO 10993-1 [1] gives a description of basic biological screening testing that may be used for predicting the safety of irradiated materials for use in medical devices. Specific tests might be required depending upon the end use of the device.

In summary, careful adherence to the guidelines in this International Standard will help the primary manufacturer to avoid problems encountered with radiation sterilization of medical devices. It is the responsibility of the device designer and primary manufacturer to ensure the suitability of the material, design and packaging for irradiation. The irradiator operator can only, if requested, advise in general terms and perform test irradiations. Primary manufacturers of medical devices are also responsible for ensuring that they are informed by suppliers of materials and components of any changes in the formulation and/or manufacturing process that could affect radiation stability.

Table A.2 lists some typical materials with good radiation stability. Table A.3 gives general guidelines to radiation stable materials.