Comparison of Biocompatibility Ion-Release Testing Methods for NiTi Medical Devices

Nickel ion-release testing has been a notified body requirement for proving the biological safety of a NiTi medical device for many years. However, most ion-release data has been collected by the medical device industry for rather short-term intervals (i.e. 7 days). Recently, FDA published the new draft guidance document 1826, requiring extended ion-release testing of at least 60 days with intermediate sampling intervals. Furthermore, a so called spike & recovery test has become mandatory, showing that the test method is appropriate to measure a known Ni-content in a solution after at least 14 days. These new requirements are posing a challenge, because according to Method B, separate stents are required for each inspection time point. Depending on the number of inspection intervals a significant amount of fully built-up and preconditioned devices is needed, resulting in huge costs. In contrast, Method A uses the very same sample for each time point, merely changing the sampling solution. The present paper reports on the practicability and results of both test methods, comparing the ion-release properties of electropolished and passively coated NiTi-stents, including competitor devices. In addition, the setup is being validated in a spike & recovery test for two different vial types.