How sensitive does chemical characterization of medical devices need to be? Calibration of analytical evaluation thresholds with the carcinogenic potency database

Abstract

Chemical characterization is a component of the safety evaluation of medical devices. An analytical evaluation threshold (AET) is recommended to calculate the required analytical sensitivity. There is a lack of consensus whether to use 1.5 or 120 μg/day in calculating the AET with the lower value often requiring sensitivities beyond analytical capabilities. The Carcinogenic Potency Database (CPDB) was reviewed to compare risks associated with using either value to calculate an AET. The TD50s for non-Cohort of Concern (non-COC) substances in the CPDB were used to extrapolate the doses to an excess cancer risk of 10−5 and calculate the total doses. The number of non-COC substances that would exceed this risk using an AET calculated using 1.5 μg/day or 120 μg/day were then compared. From the 199 substances evaluated, only two posed an excess risk at an AET calculated with 1.5 μg/day and only seven more with 120 μg/day. Furthermore, over 95 percent of non-COC substances would not pose an excess cancer risk using an AET calculated with 120 μg/day. Based on our evaluation, an AET based on 120 μg/day is protective and practical for chemical characterization of short and long-term medical devices.