CDRH Addresses Medical Device Biocompatibility Testing

A CDRH webinar has reviewed medical device biocompatibility issues addressed in a recent a guidance on “Use of International Standard ISO 10993-1 — Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing within a Risk Management Process.” The Center says the document is intended to assist industry in preparing marketing submissions for medical devices that come into direct or indirect contact with the human body in order to determine the potential for an unacceptable adverse biological response resulting from such contact. It provides further clarification and updated information on using International Standard ISO 10993-1 to support applications to FDA.

The guidance replaces Office of Device Evaluation Blue Book Memorandum #G95-1 issued in 1995. It incorporates several new considerations, including the use of risk-based approaches to determine if biocompatibility testing is needed, chemical assessment recommendations, and 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, which were not previously discussed in G95-1.

New biocompatibility testing may not be needed if the device is made of materials that have been well characterized chemically and physically in published literature, and have a long history of safe use, CDRH biomedical engineer Jennifer Goode said during the webcast. She noted that it also may be possible to leverage previously conducted biocompatibility information if:  

•              the previously tested device has similar indications, type, and duration of contact;

•              an explicit statement is provided regarding any differences in materials or manufacturing between the new and leveraged devices under consideration; and

•              information is provided to explain why differences aren’t expected to impact biocompatibility.

Goode said that if it is determined that some biocompatibility testing is needed, the guidance identifies general testing considerations for sample preparation; specific testing considerations for various biocompatibility endpoints such as cytotoxicity; and why literature is often used to assess specific endpoints such as carcinogenicity or reproductive and developmental toxicity. “In the section on sample preparation,” she continued, “we point out in the guidance document that ISO 10993-12 can be used to determine how much sample to be used... When extract studies are done, we ask for testing using both polar and non-polar solvents unless it doesn’t make sense for the device in question.”

In the genotoxicity, carcinogenicity, and reproductive developmental toxicity sections of the guidance, information is included on how to use chemical information and risk assessments instead of testing, she said. In addition, the genotoxicity section outlines the rare cases when an in vivo genotoxicity study might be considered, she added.

To view a replay of the webinar, click here. To view a transcript, click here.