FDA Draft Guidance Issued on the Use of Clinical Data in Premarket Notification 510(k) Submissions

Boston MedTech Advisors Blog, January 2024

The guidance identified the most common scenario in which clinical data may be required for 510(k) submission to determine whether the new device is as safe and effective as the predicate device:

1. Indications for use of the new device (i.e., indications for use (IFU) statement and labeling) are different from those of the predicate device, including:
   • If a currently cleared device is requesting an expanded IFU.
   • If the new device is indicated for different patient population, disease, anatomical site, structure, or pathology.
   • If the new device has a different benefit-risk profile for the proposed IFU.
2. Technological characteristics of the new device are different from those of the predicate device, including:
   • If the new device has significant changes in materials, design, energy source, etc.
3. Non-clinical testing (e.g., analytical, bench, and/or animal testing), is not adequate to establish that the new device is SE to the predicate, examples include:
   • If models are unavailable or insufficient.
   • If the model is not suitable for assessing clinical outcomes (e.g., variety of clinical environments, diverse populations).
   • If clinical evidence is required (e.g., there are specific questions that rely on clinical evidence)
4. Predicate device updated safety information includes newly identified or increased risk. [This is a new scenario not identified in previous guidance documents]
   • If FDA identifies new or increased predicate risk during their premarket review, they may request clinical data to determine whether the new device is SE.
   • FDA may learn of these new or increased risks from voluntarily reported adverse events, literature, post-market studies, recalls, etc.
   • FDA may publicly communicate such risks via safety communication, guidance, advisory committee meeting.
   • Manufacturers are encouraged not to use predicates that exhibit risk if an alternative predicate device exists without such risk.

The new draft guidance gives examples of situations when clinical data may be necessary to demonstrate SE. This is intended to enhance the predictability, consistency, and transparency of the 510(k) Program.

This draft guidance was issued in tandem with FDA’s draft guidance on “Best Practices for Selecting a Predicate Device to Support a Premarket Notification [510(k)] Submission”,³ highlighting FDA’s efforts to strengthen and modernize the premarket notification 510(k) program [See BMTA blog for more information].

The draft document has received 15 comments to date.⁴ While some comments praise FDA for their efforts to clarify when clinical data should be submitted as part of the 510(k) pathway, others are raising concerns about the implications of FDA’s proposed new approach, and the potential practical challenges associated with its implementation. Specifically, comments describe concerns that this guidance signals a shift in the longstanding review practice that may introduce unnecessary burden and overreliance on clinical data where it was previously not required. Lacking adequate explanation as to why clinical data would represent the least burdensome approach in particular scenarios, FDA reviewers might inappropriately apply the draft guidance (if finalized in its current form) to issue a request for clinical data during review of 510(k) submissions that is not grounded by the least burdensome principles and/or adequately justified. This approach may result in significant delays in the introduction of valuable products to the market and could potentially stifle innovation. FDA is in the process of considering all comments while finalizing the guidance document.

Manufacturers should carefully consider whether their 510(k) premarket submission would require clinical data to support SE to their predicate device, and are highly encouraged to contact FDA, via a Pre-submission request, to identify the level of evidence required, prior to commencing clinical trials.

About Boston MedTech Advisors (BMTA):

Since 2004, BMTA’s multidisciplinary team of highly experienced consultants has supported more than 400 medical technologies and life sciences companies around the world to achieve their business goals. BMTA assists its clients to commercialize new products and services and increase their market adoption, by addressing their unique and inter-dependent regulatory, clinical, reimbursement, marketing, and business development requirements. BMTA offers valuable, ethical, result-oriented, professional, and cost-effective insights that recognize the multi-faceted aspects of today’s healthcare markets and the client’s unique business needs.

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Reference:

1. Draft Guidance for Industry and Food and Drug Administration Staff “Recommendations for the Use of Clinical Data in Premarket Notification [510(k)] Submissions” September 2023 https://www.fda.gov/media/171837/download
2. Guidance for Industry and Food and Drug Administration Staff “The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]” July 2014. https://www.fda.gov/media/82395/download
3. Draft Guidance for Industry and Food and Drug Administration Staff “Best Practices for Selecting a Predicate Device to Support a Premarket Notification [510(k)] Submission” September 2023 https://www.fda.gov/media/171838/download
4. https://www.regulations.gov/docket/FDA-2023-D-3133/comments

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