October 8, 2020
Minor updates to have little impact on manufacturers
The U.S. Food and Drug Administration (FDA) issued the updated guidance document, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process," on September 4, 2020, to provide further clarification on the use of ISO 10993-1 to support PMA, HDE, IDE, 510(k), and De Novo submissions. The updated guidance document is very similar to the version issued in 2016, so this update will not impact the approaches taken by medical device manufacturers over the past few years to evaluate the potential biological response resulting from contact of the device with the body. There are some minor changes in the newly issued version, which are outlined below:
- The new version was issued by the FDA Center for Devices and Radiological Health (CDRH) and the Center for Biologics Evaluation and Research (CBER), whereas the previous version was issued only by CDRH.
- Under Section II (page 8), the phrase "biologic-device combination products" is used instead of simply "biologic" as in the 2016 version.
- FDA cites a different reference in footnote 16 (page 8): "Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices: Guidance for Industry and Food and Drug Administration Staff" from 2018 versus "Guidance for Industry and FDA Staff — Recognition and Use of Consensus Standards" referenced in the 2016 version. The link to the latter no longer exists; hence, the reference has been updated.
- Under Section III C (page 12), there is an additional footnote that states, "FDA supports the principles of the '3Rs,' to reduce, refine, and replace animal use in testing when feasible. We encourage sponsors to consult with us if it [sic] they wish to use a non-animal testing method they believe is suitable, adequate, qualified for use with medical devices, and feasible. We will consider if such an alternative method could be assessed for equivalency to an animal test method." This footnote was not included in the previous version of the guidance; however, this does not appear to signal a change in FDA's opinion on testing, since both versions state, "In order to reduce unnecessary testing, including animal testing, FDA recommends that sponsors consider all available relevant information when conducting their risk assessment."
- In the Thrombogenicity subsection (VI. B) FDA refers to the updated ISO 10993-4 "Selection of tests for interaction with blood" standard from 2017 (compared to 2002 in the previous version) in footnote 44 on page 36.
How Exponent can Help
Exponent's multidisciplinary team of toxicologists, biomedical engineers, and materials scientists has experience conducting testing and risk assessments to help clients address biocompatibility requirements. Our team routinely evaluates the safety and biocompatibility of device materials and any potential impacts on changes to medical devices. Exponent has extensive experience in the following:
- Assisting clients in testing strategy for medical device biocompatibility requirements for FDA Premarket Applications (PMAs), Humanitarian Device Exceptions (HDEs), Investigational Device Applications (IDEs), and Premarket Notifications (510(k)s).
- Performing chemical characterization studies to identify extractable/leachable substances using a variety of analytical techniques according to ISO 10993 standards.
- Conducting toxicological risk assessments based on the results of chemical characterization testing and preparing reports for regulatory submissions.
- Evaluating and summarizing conclusions on the overall biocompatibility of a device (or device component) based on literature searches and existing in vitro and in vivo data.
- Performing data gap analyses to aid clients in decisions on biocompatibility endpoints for testing.
- Conducting data gap analyses based on the identified extractables/leachables to determine the feasibility of a risk-based approach in biocompatibility assessments.