Toxicological Risk Assessment (TRA)

Evaluating the potential health risks associated with exposure to leachable impurities, contaminants, or other residues in a medical device or drug product.

The Toxicological Risk Assessment (TRA) is a research-based evaluation comprised of four activities:

  1. hazard identification and data evaluation
  2. exposure assessment
  3. dose-response analysis
  4. risk characterization

The risk assessment is based on a chemical characterization of the test article, published information from the toxicological literature, and tolerable exposure limits, which may be adopted from published guidelines or derived on the basis of available toxicology data. The methods for toxicological risk assessment are, in general, described in ISO 10993-17, ISO 18562, ICH M7 and Q3D guidance; however, the risk assessment must consider special topics and regulatory guidance which may be published on specific devices.

The objective of a toxicological risk assessment is to evaluate the potential health risks associated with exposure to leachable impurities, contaminants, or other residues in a medical device or drug product. Based on the data from a chemical characterization, the risk assessment is to make a determination as to whether the release of chemicals during the use of a medical device or drug formulation may represent a toxicological risk that is unacceptable from a regulatory perspective.

Regulatory Guidance

  • ISO 10993-1: Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing within a Risk Management Process
  • ISO 10993-17: Biological Evaluation of Medical Devices – Part 17: Establishment of Allowable Limits for Leachable Substances
  • ICH Q3D. 2015: Elemental Impurities: Guidance for Industry, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER)
  • ICH M7. 2015: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, Guidance for Industry
  • ISO 14971, 2007: International Standard. Medical Devices- Application of Risk Management to Medical Devices. Second Edition. Reference Number ISO 14791:2007(E).
  • ISO 18562: Biocompatibility Evaluation of Breathing Gas Pathways in Healthcare Applications