By: Claus Soendergaard, Senior Manager of Biocompatibility
On September 8th 2023, FDA issued an updated version of their primary biocompatibility guidance, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process". This marks the first update to the guidance since 2020, making it important to explore the revisions and their potential implications for future biocompatibility assessments.
While the updated guidance provides additional clarity on FDA’s thinking on biocompatibility and offers some much-anticipated opportunity to lessen the testing burden for certain device with intact skin contact, biocompatibility still commands significant time and resource commitments throughout the medical device life cycle. That is why you can rely on MCRA’s team of expert regulatory and biocompatibility specialists to help you navigate the intricacies of this updated guidance and your biocompatibility needs in general to expedite your product's market entry and patient access.
Key Updates
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Attachment G: The previous 2020 Draft Guidance on Biocompatibility of Certain Devices in Contact with Intact Skin has been incorporated as a new Attachment. Probably the single most important update to the guidance and thus deserving of a more detailed review below.
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The previous reference to ‘US-marketed medical devices’ has been changed to ‘marketed medical devices’, possibly implying openness to consider biocompatibility evidence from devices marketed outside of the US.
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While FDA has always been in support of reducing animal use where valid alternative methods exist, physical, morphological and topographical characterization testing is now specifically called out as alternative methods by which biocompatibility may be addressed outside of in vivo testing.
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More detailed recommendations are provided for how to justify the use of data not obtained in compliance with GLP regulations.
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Reference to ’recognized standard’ has been updated to ‘FDA-recognized consensus standard’. The emphasis on using FDA-recognized consensus standards is now more clearly stated. Use the following link to check if a given standard is recognized by the FDA, and to what extent: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/search.cfm
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Genotoxicity testing for extracorporeal circuits was previously only called out in the footnotes to Table A.1. Additional details have now been added to the main genotoxicity section.
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It’s noted that carcinogenicity is typically addressed via a risk assessment (as opposed to direct testing).
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Table A.1 is now more closely aligned with the corresponding Table A.1 of ISO 10993-1:2018 with a couple of exceptions:
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Unlike ISO 10993-1, FDA still requires material medicated pyrogenicity testing of devices with prolonged and long-term contact with mucosal membranes.
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Whereas ISO 10993-1 provides separate columns for subacute and subchronic systemic toxicity, the updated FDA guidance has these endpoints combined with the note that sponsors should set duration based on intended use, e.g., a device with an intended use longer than 14 days should not be assessed by a 14-day test. This update brings some clarity to the expectations for these two endpoints where it was not previously obvious if one or the other or both were expected for devices where this endpoint is applicable.
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The option to include only summary test reports from ASCA accredited test labs is provided.
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The term ‘permanent implant’ has been replaced with ‘long term’ in agreement with the terminology if ISO 10993-1:2018 as well as other smaller updates to align with current standard revisions.
Attachment G: Biocompatibility of Certain Devices in Contact with Intact Skin
The Inclusion of Attachment G is significant in that FDA previously required sponsors to address the endpoints of cytotoxicity, sensitization, and irritation for all devices with intact skin contact, essentially regardless of their materials of construct. Sponsors could easily overlook this expectation for e.g., wearable accessories or external device interfaces constructed from materials that most people already interact with daily. Whether addressed prospectively or in response to deficiencies, biocompatibility testing for such materials were typically expensive and time consuming, as well as often technically very challenging due to e.g., absorptive properties of foam and fabrics or inclusion of elastomers like elastane (Lycra/Spandex).
With the new Attachment G, sponsors now have a clearer path to address biocompatibility of many common polymers and fabrics that come into contact only with intact skin, using a risk assessment-based approach in lieu of biological endpoint testing. This can be a significant benefit to sponsors because this can potentially both reduce lead time and cost for addressing biocompatibility, but it also is likely to greatly reduce the need for animal testing of materials that we already know to be safe.
The previous Draft Guidance on Biocompatibility of Certain Devices in Contact with Intact Skin from October 2020 appears to have been incorporated with only a few changes, mainly updates to the list of applicable materials and a provision that processing chemicals and additives generally will not need to be disclosed except for color additives. This specific mention of color additives is not further clarified, and it remains to be seen how problematic this requirement may be for sponsors who are relying on more off-the-shelf solutions where they would have limited control of the choice of color additives.
The possibility of omitting endpoint testing for devices and device components with intact skin contact is exciting news for sponsors, however, it’s important to remember that only a subset of devices and materials fall within the scope of the guidance. One of the several exclusions listed in the guidance could still place you on the path of a more traditional biocompatibility assessment. Equally important, even if your device and device materials are within the scope of the guidance, the requirements for documenting safety in absence of endpoint testing are not trivial.
Learn more about MCRA’s Biocompatibility services and how we can assist you with this new guidance.