Over the past several years, FDA has faced criticism stemming from high-profile device issues related to materials, including the Essure permanently implanted birth control device and metal-on-metal hip implants. Given this, it is not surprising that device biocompatibility has received greater focus in FDA premarket reviews for medical devices. FDA initially issued Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” (Guidance) in 2016 to provide guidance to sponsors of premarket applications on evaluation of biological risk and biocompatibility testing for devices that are in direct or indirect contact with the human body. However, many device sponsors have continued to face challenges demonstrating device biocompatibility, with many sponsors receiving additional information requests related to the biocompatibility data necessary to support a marketing application. The Guidance describes a risk-based approach where justification may be provided to support the overall testing strategy and interpretation of results. Many additional information requests that we have seen relate to disagreements between FDA and the sponsor with respect to justifications provided by the sponsor on what tests are applicable to the device, how the device tested is representative of the device intended for commercialization, the impact of differences between device tested and the device intended for commercialization, test methods, especially for extraction, and interpretation of results.
On March 19, 2021, FDA announced the launch of an online Biocompatibility Assessment Resource Center to provide more clarity for sponsors navigating biocompatibility requirements. The new resource is intended to explain terms and concepts for use in conjunction with the Guidance. The site is divided into four steps: 1) Biocompatibility Basics, 2) Evaluation Endpoints, 3) Test Articles, and 4) Test reports.
Biocompatibility Basics provides a very high-level description of the basis for biocompatibility and a glossary of biocompatibility terms. In some ways, it is a repackaging of the Guidance. The Basics page describes devices for which biocompatibility information is needed, what FDA assesses or evaluates, how FDA assesses or evaluates biocompatibility and biocompatibility factors of interest to FDA. In the glossary, there is quite a bit of overlap in terms defined compared to the Guidance, with some new terms added, most of which come from the ISO 10993 series of biocompatibility standards.
Evaluation Endpoints provides the same information as Attachment A of the Guidance in an easy-to-use format. One statement of note is that FDA indicates that device categorization information can be obtained informally via e-mail or as part of the pre-submission process. Information on Test Articles includes the same information as Attachment F of the guidance, providing example text to use when relying on biocompatibility data from a test article that is not the final, finished device, e.g., when using an identical material to that used in another cleared device. Information on Test Reports includes the same information as Attachment E of the Guidance.
While these resources may prove helpful to those new to biocompatibility, for those familiar with the Guidance, there is not likely much value other than the convenient format and it is not likely to help resolve the biocompatibility challenges faced by sponsors during premarket review. It is nice to see informal e-mail mentioned as a way to get questions answered, but use of the Guidance and the pre-submission process will continue to be the best way to determine testing necessary to support a device’s biocompatibility before conducting studies.