Study Design

Assisting you in the strategic design of biocompatibility safety evaluations that meets the requirements of ISO 10993

Biocompatibility in a Risk Management Context

As part of a biocompatibility evaluation, ToxSmart reviews the design and intended use of a medical device, as well as the previous biocompatibility data for the device or a similar device. Based on this assessment, we provide our recommendations for completion of the biological safety evaluation, which may include:

  • traditional in vivo and in vitro biocompatibility tests
  • chemical characterization, including extractable / leachable analysis
  • toxicological risk assessment

ToxSmart can assist you in the strategic design of a biocompatibility test plan that addresses the concerns and meets the requirements of ISO 10993-1 and the FDA guidance on the use of ISO 10993-1.

Chemical Characterization: Extractables and Leachables

Risk assessment is based on data from chemical characterization; ToxSmart can assist with the design of chemical characterization studies or extractable / leachable studies. This ensures that the resulting data is relevant for estimating a daily exposure to the patient based on the intended clinical use of the device.

The objective of the extractable / leachable analysis is to identify and quantify all substances that may be released from a test article during clinical use and in practical terms, is comprised of incubations of the test article in various media, e.g., water, ethanol, or hexane, at specific temperatures and durations. However, the choice of conditions and extraction media should be made in the context of risk assessment. Early involvement of ToxSmart risk assessors in the design of chemical characterization studies can help identify the correct approach for your study.

ToxSmart risk assessors also provide analytical evaluation thresholds (AET) to chemistry laboratories, which can optimize in the E/L analysis. We can also help by identifying the most important analytes, and determine limits of detection for leachability studies.

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