Optimization of the Nonclinical Biological Evaluation of Medical Devices Using Toxicologic Pathology Best Practices.

Abstract

Innovation in the medical device industry is challenging due to the increasing physicochemical, structural, and engineering complexity of devices; proliferation of combination products; advent of long-term implants; and variable approaches to assessing tissue reactions. Nonclinical evaluation of biological responses to implanted devices requires careful study design and implementation of pathology practices to obtain the best data for translating device-related tissue reactions ("toxicity") and associated procedure-induced effects to predict possible outcomes in human patients. This paper outlines optimal pathology practices and related regulatory considerations that frame the nonclinical interpretation of biological responses induced by medical devices and combination products. These pathology practices have been developed by expert pathologists with extensive experience in medical device evaluation to address current guidance found in existing ISO Series standards, regulatory documents, and globally accepted "best practice" recommendations for toxicologic pathology assessment of therapeutic entities. Accordingly, the practices in this paper provide an optimized framework for biological evaluation of tissue responses to medical devices and combination products (both degradable and permanent devices) that should improve the relevance and utility of animal safety data provided to health authorities for human risk assessment.