Genotoxicity evaluation of medical devices: A regulatory perspective.

This review critically evaluates our current regulatory understanding of genotoxicity testing and risk assessment of medical devices. Genotoxicity risk assessment of these devices begins with the evaluation of materials of construction, manufacturing additives and all residual materials for potential to induce DNA damage. This is followed by extractable and/or leachable (E&L) studies to understand the worst case and/or clinical exposures, coupled with risk assessment of extractables or leachables. The TTC (Threshold of Toxicological Concern) approach is used to define acceptable levels of genotoxic chemicals, when identified. Where appropriate, in silico predictions may be used to evaluate the genotoxic potentials of identifiable chemicals with limited toxicological data and above the levels defined by TTC. Devices that could not be supported by E&L studies are evaluated by in vitro genotoxicity studies conducted in accordance with ISO10993-3 and 33. Certain endpoints such as 'site of contact genotoxicity' that are specific for certain classes of medical devices are currently not addressed in the current standards. The review also illustrates the potential uses of recent advances to achieve the goal of robust genotoxicity assessment of medical devices which are being increasingly used for health benefits. The review also highlights the gaps for genotoxicity risk assessment of medical devices and suggests possible approaches to address them taking into consideration the recent advances in genotoxicity testing including their potential uses in biocompatibility assessment.