The Diagnostics Pipeline: FDA Moves to Modernize 510(k) Process for New Lab Tests & Devices

On September 7, the FDA published three draft guidances proposing fundamental alterations to the 510(k) pathway it uses to clear in vitro diagnostic tests and other medical devices. The changes aim to speed up the process and place less emphasis on older predicate products in deciding whether to grant premarket clearance to new devices, while still ensuring products’ safety.

The diagnostic challenge

Section 510(k) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) requires manufacturers to submit a premarket notification to the FDA at least 90 days before introducing a new device intended for human use to the market for commercial distribution. The manufacturer must demonstrate in the 510(k) marketing submission that the device is substantially equivalent to a “predicate device” in accordance with section 513(i) of the FD&C Act by essentially comparing the two devices in terms of use, technology, safety, health, and other criteria listed in the statute. The agency then reviews the submission to determine whether the product meets the criteria for market clearance.¹

The issue with this approach is that predicate devices may be decades old, considering that the FDA has been clearing medical devices since 1976. “Data show that nearly 20 percent of current 510(k) [clearances] are based on a predicate [device] that’s more than 10 years old,” according to the agency.² In 2018, the agency issued a Medical Device Safety Action Plan for updating the 510(k) pathway to account for advances in medical technology. “As device technology continues to evolve and the types of medical devices expand exponentially, we are mindful that the ways in which we assure reasonable device safety must also keep pace,” the plan noted.³

The new FDA 510(k) draft guidance

The three new draft guidances are the culmination of more than five years of FDA 510(k) modernization efforts, covering:

1. Selection of predicate devices

The draft guidance on selection of predicate devices for use in a 510(k) premarket submission comparison asks manufacturers to base their selection on the quality of evidence used to clear those predicate devices, as well the devices’ performance history since entering the market, especially in terms of unresolved safety issues and design-related recalls.⁴

Recommended best practices: Manufacturers should use the agency’s FDA 510(k) Premarket Notification Database to gather basic information necessary to identify potentially valid predicate devices that may serve as the basis of comparison, including but not limited to the trade names, manufacturers, and 510(k) numbers of similar devices. In selecting the predicate device, manufacturers should look for:⁵

• devices that were cleared using “well-established methods,” including those from an “FDA-recognized voluntary consensus standard, FDA guidance document, qualified medical device development tool (MDDT) or a widely available and accepted method published in the public domain or scientific literature”;
• devices that continue to meet or exceed safety standards during use in their intended environment, giving consideration to recalls, adverse events, and material changes that occurred after the device reached the market;
• devices that do not have “unmitigated use-related or design-related safety issues,” based on “consideration of emerging signals or safety communications”; and
• devices that have not been subject to a “design-related recall.”

2. Use of clinical data

The draft guidance on use of clinical data says that data to support a 510(k) notification should constitute “valid scientific evidence,” which may include, but aren’t limited to:⁶

• results of pre and postmarket clinical investigations of the device, i.e., clinical trials;
• results of pre and postmarket clinical investigations or other studies of comparable devices reported in the scientific literature;
• unpublished reports about the clinical experience of the new device or a comparable device; and
• registries, adverse event databases, medical records—such as electronic health records or claims—and other sources of data about the device or predicate device’s clinical performance.

The draft guidance also lists detailed scenarios illustrating situations when manufacturers must back their 510(k) submissions with clinical data demonstrating the equivalence of the new device to an existing predicate. An example of such a situation is when there are technological differences between the devices or nonclinical testing alone is inadequate to establish equivalence.

3. Evidentiary expectations for implant devices

The third draft guidance sets out evidentiary expectations for implant devices under the 510(k) process. The FD&C Act regulations (21 CFR 860.3(d)) define an implant as “a device that is placed into a surgically or naturally formed cavity of the human body” for 30 days or more. Accordingly, this draft guidance has only limited relevance to laboratory tests.⁷

Takeaway

Issuing draft guidances is an “important step in our ongoing commitment to optimize the clarity, predictability, and consistency of the 510(k) Program,” noted Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health (CDRH), in a statement accompanying the release of the proposals.⁸ The initiative also advances the FDA’s efforts to implement its commitment under the 2022 Medical Device User Fee Amendments (MDUFA V) agreement to cut the time the agency takes to decide on 510(k) submissions from the current 128 calendar days to 112 calendar days by 2027. The agency’s ultimate objective is to eventually issue decisions on 95 percent of submissions within 90 days.^9,10

The FDA will be taking public comments on the new draft guidance materials through December 6. It will then finalize the guidances based on the feedback.

References:

1. https://uscode.house.gov/view.xhtml?req=(title:21%20section:360c%20edition:prelim)
2. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-jeff-shuren-md-director-center-devices-and
3. https://www.fda.gov/media/112497/download
4. https://www.fda.gov/media/171838/download
5. https://www.fda.gov/medical-devices/510k-clearances/search-releasable-510k-database
6. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-use-clinical-data-premarket-notification-510k-submissions
7. https://www.fda.gov/media/171835/download
8. https://www.fda.gov/medical-devices/medical-devices-news-and-events/cdrh-statement-fda-continues-take-steps-strengthen-premarket-notification-510k-program
9. https://www.fda.gov/media/157074/download?attachment
10. https://www.g2intelligence.com/congress-passes-new-fda-medical-devices-user-fee-amendments-mdufa-v-deal/

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Here are the key new laboratory testing and diagnostic product clearances that were announced in the period between mid-August 2023 and early October 2023:

New FDA Approvals & Emergency Use Authorizations (EUAs)

New CE marks and global certifications

Notable European CE certifications announced during the period:

New Approvals in Europe

Other international clearances announced during the period: