Background

Since 2009, the average page count of a 510(k) premarket notification submission to the 510(k) Program has more than doubled, to over 1,000 pages, partially as a result of updated FDA policies surrounding premarket submission content requirements, and because medical devices are growing more complex and innovative. As a result, over the past 10 years, CDRH has worked to modernize the 510(k) Program, starting with an evaluation and set of recommendations for improvements, which were implemented as described in a November 2018 performance report.

Also in November 2018, CDRH proposed transformative new steps to modernize the 510(k) Program to advance the review of the safety and effectiveness of medical devices. Then, in January 2019, CDRH requested public feedback on these steps to continue to modernize the framework for 510(k) review. Responding to these comments, and building on the agency’s “Medical Device Safety Action Plan,” FDA has issued three new draft guidances that propose recommendations on best practices for selecting a predicate device, situations when clinical data may be necessary in a 510(k) submission, and evidentiary expectations for 510(k) submissions for implanted devices.

Best Practices for Selecting a Predicate Device to Support a Premarket Notification [510(k)] Submission

The first draft guidance recommends best practices for selecting a predicate device. The guidance introduces the concept of “valid predicate devices” (devices with the same intended use which do not have different questions of safety and effectiveness), and the subset of those valid predicate devices which are selected using best practices. In addition to considering predicate age, which FDA has more recently noted was an important factor, the draft guidance identifies additional factors relevant for selecting a predicate device including that it:

• was cleared using well-established methods;

• meets or exceeds expected safety and performance, taking into account new information that may be available since clearance;

• does not have unmitigated use-related or design-related safety issues; again taking into account new information that may be available since clearance and,

• is not associated with a design-related recall.

This draft guidance explains how use of these best practices is expected to benefit manufacturers, FDA, and public health, and it provides examples of how to apply these best practices. For example, FDA recommends that companies review medical device safety communications and reports of injuries, deaths, and malfunctions in the public medical device reporting (MDR) and complaint databases. Recalls and MDRs may impact the appropriateness of a device predicate, and further may inform the company on potential issues that are likely to arise during review with regard to risk mitigation.

FDA further suggests submitters consider how much information is available regarding the test methods used in support of the predicate device’s 510(k) clearance and whether those methods continue to be appropriate for evaluating the subject device. When a sponsor is selecting between two similar valid predicate devices, where one identified performing testing using FDA guidance and recognized voluntary consensus standards while the other did not, FDA recommends the sponsor select the valid predicate device in which testing relied on FDA standards. While this is a reasonable recommendation, it may not always be a practical one given that in many cases, information on the methodology used to test a predicate device is not available to other companies via the 510(k) Summary.

FDA also states in the draft guidance that to increase transparency with regard to predicate devices, the agency will emphasize that there needs to be sufficient information provided in the publicly released 510(k) summary published with clearance of the device “to provide an understanding of the basis for a determination of substantial equivalence.” The 510(k) Summary should also include a discussion of how the best practices were used to select the predicate device. When a company cannot identify a valid predicate that meets the best practices, FDA recommends they state this in the 510(k) Summary and also explain any performance testing they conducted to address safety or effectiveness concerns with the chosen predicate.

Recommendations for the Use of Clinical Data in Premarket Notification [510(k)] Submissions

The second draft guidance aims to provide transparency on when clinical data may be required to demonstrate substantial equivalence in a 510(k) submissions, clarifying and building upon the recommendations in FDA’s July 2014 510(k) Program guidance:

1. When there are differences between the indications for use of the new device and the predicate device: in this case, the draft guidance points to differences in the patient population, the disease, or the anatomical site, structure, or pathology as possible factors that might make clinical data necessary for a demonstration of substantial equivalence.

2. When there are differences between technological characteristics of the new device and the predicate device: FDA states that clinical data may be necessary if there are significant changes in materials, in device design, in energy source, or in other device features.

3. When the substantial equivalence between the new device and the predicate device cannot be determined by non-clinical testing, such as analytical, bench, or animal testing: the draft guidance indicates the agency will consider whether there is a model available or if the available model may not be adequate because it has certain limitations that do not allow for an adequate assessment, may not be predictive of clinical outcomes, or when there are anatomical and/or pathophysiological species-specific questions that rely on clinical evidence.

The 2023 draft guidance also adds a fourth scenario, clarifying that, when a newly identified or increased risk for the predicate device is identified, clinical data may be needed to make a determination of substantial equivalence.

This guidance addresses a topic of critical importance to sponsors, given the resources required to conduct a clinical study, and one where guidance has been lacking in the past. The new draft guidance does not make reference to FDA’s SOP: Decision Authority for Additional or Changed Data Needs for Premarket Submissions, which outlines when clinical data can be requested for device types which have not required clinical data in the past. Thus, it is not clear, when final, whether the recent guidance will replace or be compatible with that policy.

Evidentiary Expectations for 510(k) Implant Devices

The third draft guidance aims to enhance predictability for sponsors in preparing 510(k) submissions for implants and promote consistency in review of such devices, purporting to:

• serve as a primary resource on general expectations for all 510(k) implant devices, in addition to device-specific guidances which provide further specificity for a given device type;

• assist industry in design and execution of appropriate performance testing to support 510(k) submissions for implant devices;

• provide recommendations for content and labeling to include in 510(k) submissions for implant devices; and,

• convey that FDA considers the patient experience to be paramount in improving implant device safety, and encourages the collection, analysis, and integration of patient experience data for implants to support 510(k) submissions for those devices.

The draft guidance discusses review considerations that apply to all implanted devices reviewed through the 510(k) Program, suggesting set evidentiary expectations for such devices including non-clinical recommendations, human factors and usability, clinical performance testing, patient experience information, labeling, and other recommendations.

The guidance acknowledges that testing requirements will vary based on the intended use of the implants, but discusses general considerations that may be applicable to all implants. While the guidance specifies it is for “510(k) Implants”, the majority of the guidance would seem to be applicable to implants that are reviewed through other FDA regulatory pathways (de novo, PMA, HDE) as well.

eSTAR electronic templates

Additionally, as part of FDA’s efforts to modernize the 510(k) Program and implement MDUFA V, starting October 1, 2023, all original 510(k) submissions must be submitted as electronic submissions using eSTAR, as noted in September 2022 final guidance on Electronic Submission Template for Medical Device 510(k) Submissions. eSTAR is the only available electronic submission template to facilitate the preparation of 510(k) electronic submissions.

Next steps

On October 26, FDA will host a webinar for industry and other stakeholders to discuss these draft guidances and FDA's ongoing efforts to modernize the 510(k) Program. The agency is also accepting comments on each of the draft guidance documents through December 6, 2023.