FDA Updates Guidance on ISO 10993-1 for Evaluation of Biocompatibility

The FDA has updated its guidance, Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process,” to provide further clarification and updated information on the use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” to support applications to FDA. The guidance is intended for use in Premarket Applications (PMAs), Humanitarian Device Exceptions (HDEs), Investigational Device Applications (IDEs), Premarket Notifications (510(k)s), and De Novo requests for medical devices that come into direct contact or indirect contact with the human body in order to determine the potential for an unacceptable adverse biological response resulting from contact of the component materials of the device with the body.

The new guidance includes recommendations on the use of risk-based approaches to determine if biocompatibility testing is needed, chemical assessment recommendations, recommendations for biocompatibility test article preparation for devices with submicron or nanotechnology components and for devices made from in situ polymerizing and/or absorbable materials, and biocompatibility recommendations when certain materials only contact intact skin.

The FDA guidance follows the seven general principles of ISO 10993-1’s approach to biocompatibility evaluation, with minor deviations and/or clarifications including:

In relation to the requirement to provide the chemical formulation for each component material, the FDA states that “in situations where details pertaining to the materials of manufacture may be proprietary information held by the material supplier, a master file for the material component(s) may assist in determining the formulation of some components of the final device.”
ISO 10993-1 dictates that any in vitro or in vivo biological safety experiments or tests should be conducted in accordance with recognized Good Laboratory Practice (GLP) regulations. For the purposes of submission to the FDA, if information on these types of nonclinical laboratory studies is provided, a statement that all such studies have been conducted in compliance with applicable requirements in the Good Laboratory Practice regulation in 21 CFR 58 should also be provided. If any such study was not conducted in compliance with such regulation (e.g., for supporting historical data included with a regulatory submission), FDA recommends you include a statement in your submission explaining the reasons why the study was not in compliance with the GLP Regulations, as well as a detailed description of all deviations from the regulation.
When test data are provided, complete experimental data, complete to the extent that an independent conclusion could be made, should be submitted to the reviewing authority. For the purposes of submission to the FDA, if testing is conducted according to an FDA-recognized consensus standard that does not include data reporting, submission of the test data is optional.