New US FDA Guidance on the Use of International Standard ISO 10993-1: Top 10 Changes

As anticipated, the United States Food and Drug Administration (US FDA) issued a new guidance document on the use of ISO 10993-1 on June 16, 2016. In one statement the FDA summarizes how they want to see biocompatibility for medical devices supported: “For FDA submissions, biocompatibility information for the device in its final finished form, either developed through the risk management process or from biocompatibility testing (using both in vitro and in vivo models), and/or adequate chemical characterization in conjunction with supplementary biocompatibility information that adequately address the biocompatibility risks of the device should be provided.”

The guidance document doubled in length over the previous draft – there is a lot of new information. Here are our top 10 highlights:

  1. Device Examples: This version includes more communication and examples to support device companies in their submissions. Evidence is in the 5 additional attachments and the 30 page increase over the previous draft.
  2. Practitioner Contact: Assessing risk based on practitioner contact with devices now falls under ISO 10993-1 which expands the scope beyond patient safety.
  3. Recognized Standards: Important to note US FDA references other standards that are relevant to biocompatibility testing (ASTM, OECD, ICH and USP).
  4. Risk Management Guidance: Section III Risk Management for Biocompatibility Evaluations is a new lengthy 10 page section with great examples and discussion of how to approach and assess risk.
  5. Decision Trees: As described in the document assess risk BEFORE testing begins. This should be laid out in a Biological Evaluation Plan.
  6. FDA ISO Biocompatibility Matrix Updates: FDA Modified matrix is “…not a checklist…” Added separate column for Material-Mediated Pyrogenicity.
  7. Cytotoxicity Tests: Extraction time for cytotoxicity testing is identified as 24-72 hrs extraction. This differs from ISO 10993 and possibly implies that all permanent implants should be extracted for longer periods (72 hours).
  8. Hemolysis Tests: Only indirect hemolysis testing is now allowed for devices with indirect blood contact. Complement Activation no longer requires analysis of C3a. Serum is now preferred over plasma.
  9. Genotoxicity Tests: Genotoxicity testing may be waived if chemical characterization testing and literature research indicate that a genotoxic risk does not exist. However genotoxicity testing and research cannot be used to mitigate carcinogenic risk.
  10. Pyrogenicity Tests: Pyrogenicity testing is expanded to include the Bacterial Endotoxin Test (BET) for sterile devices having direct/indirect contact with the cardiovascular system, lymphatic system or Cerebral Spinal Fluid (CSF) regardless of contact duration.

Look for our webinar early August where we will go over these highlights and so much more. The FDA is presenting a webinar on the new guidance document on July 21st. If you have any questions or concerns in the meantime, contact our Toxicology and Biocompatibility experts in the Nelson Laboratories technical consulting group.

Audrey Turley – Research Scientist

Thor Rollins – Biocompatibility Expert

Dr. Sarah Campbell – Toxicologist

Trevor Fish – Toxicologist

Dr. Matthew Jorgensen – Material Science

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