The analytical evaluation threshold for inorganic metal extractables and leachables analysis of medical devices

Abstract

Chemical characterization of medical devices uses the analytical evaluation threshold (AET) to determine reportable organic extractables, as these chemicals may be of toxicological concern and should be addressed via toxicological risk assessment. The AET is not applicable to metal extractables due to the exclusion of toxicity data on inorganics from the dataset used to derive dose-based threshold (DBT) values. This results in minimal guidance for reporting metal extractables. Herein, an AET for metals, or mAET, is proposed as a reporting threshold for individual metal extractables. The mAET can ensure metals are reported that are at quantities that may present a patient safety risk. This may reduce the number of metals reported in a chemical characterization report, improving the efficiency of the overall biocompatibility evaluation by removing unneeded effort and resource time. Conversely, an analytical method’s ability to report all metals at toxicologically relevant levels can be confirmed by comparing method sensitivity to mAET values. DBTs were developed for 70 metals, permitting mAET values to be determined. These mAET values were then compared to metal reporting limits from 13 previously conducted chemical characterization studies, which used varying extraction designs and analytical methods, to determine the impact of the mAET.