Skip to main content

The FDA issued a long-awaited final guidance Use of International Standard ISO 10993-1, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process replacing the historical “Blue Book Memorandum #G95-1” (1995). The new guidance, released in June, is a substantial upgrade from its predecessor and serves the purpose of guiding the use of ISO 10993-1.

The most notable change of the guidance is the emphasis on employing an overall risk management approach to the biocompatibility evaluation of a medical device. The FDA also acknowledges in the new guidance the scientific advancements in test methods—such as chemical assessments— which may result in the reduction of biocompatibility testing, including the use of animal based studies.

QA Consulting has outlined five key points from the new guidance and recommendations:

  • Biocompatibility Endpoints for Evaluation: Use ISO 10993-1 and the FDA modified matrix (Attachment A) to determine the relevant biocompatibility endpoints for an evaluation.
  • Considerations for Labeling Devices as “-free”: The FDA warns that existing test methods may not reliably determine that a device is completely “free” of a substance. Manufacturers should revisit labeling claims or any statement of a product being substance “-free” (i.e. “latex-free”, “BPA-free”, “pyrogen-free”). The FDA recommends that manufacturers use the phrase “not made with (substance).”
  • Device Master Files for Biocompatibility Evaluations: The FDA also expresses a concern that device master files may not appropriately address all of the characterization or biocompatibility questions that pertain to the medical device in its final finished form and has provided Attachment B as an additional resource.
  • Biocompatibility Testing Considerations: Incorporate a thoughtful approach to test article preparation to most closely represent use of the medical device.
  • Specific Considerations for the following Testing: cytotoxicity, sensitization, hemocompatibility, pyrogenicity, implantation, genotoxicity, carcinogenicity, reproductive and developmental toxicity, and degradations assessments.

What is not included in this guidance that was previously included in a draft version released in April 2013, is devices that come in contact with gas pathways and color additives. In response to comments, the FDA announced that these types of devices will be covered separately.

For assistance with performing medical device biocompatibility evaluations and in opening discussions with the FDA, please contact us at 512-328-9404 or by e-mail at