Getting Started with the FDA’s New LDT Rule

By now, most US clinical labs are familiar with the FDA’s final rule on laboratory-developed tests (LDTs).¹ But, with hundreds of pages of regulations to consider, the question on most lab professionals’ minds is: where do we start?

In our May 30 webinar, “Key Things Labs Need to Know About the FDA’s Final LDTs Rule,” speakers Shannon Bennett (director of regulatory affairs, Department of Laboratory Medicine and Pathology, Mayo Clinic) and Julie Ballard (principal, Carrot Clinical) outlined the phase-in process for the new regulations, key considerations, and steps labs can take to ensure they’re prepared.

Planning your phase-in

Stage 1 (May 6, 2025)

“Laboratories will need to identify, investigate, address, and report potentially adverse events to the FDA—and document every aspect of this,” Bennett explained. However, questions remain regarding which adverse events the FDA expects to see. “If an event is due to a defect in your tests or something missed in the development of a test, the FDA will want to hear about it. If you modify your test or take it off the market due to a defect, that needs to be reported as well. If your laboratory receives a complaint about one of your tests, you need to investigate and potentially submit that complaint to the FDA.”

Stage 2 (May 6, 2026)

“Laboratories need to register as medical device manufacturers,” said Bennett, “but we’re going to need some guidance from the FDA on how registration will work.” Labs will also need to list specific information about their LDTs in a public database and adhere to labeling requirements.

“What does labeling mean in the context of an LDT, which is not a physical thing?” Bennett asked. He noted that the FDA’s interpretation includes information on a test’s performance (accuracy and precision) and a validation summary, potentially constituting a significant clerical burden for labs. That’s exacerbated by the need to adhere to investigational use requirements, which means that labs whose LDTs are used in the context of a clinical trial may need to submit an Investigational Device Exemption to the FDA.

Stage 3 (May 6, 2027)

Quality system requirements come into place at this point. Bennett explained that, although labs aren’t required to be Good Manufacturing Practices-certified, they must meet select requirements: design controls, purchasing controls, acceptance activities, and CAPA (Corrective Action Preventive Action).

Stage 4 (November 6, 2027)

“Laboratories will need to submit all high-risk LDTs to the FDA unless they’re exempt or under enforcement discretion,” Bennett said, but noted that the FDA plans to reclassify most high-risk (Class III) LDTs as moderate-risk (Class II). “The million-dollar question is: what is high-risk?”

The FDA assesses risk through a predicate device—a similar, legally marketed medical device. Tests that are equally safe and effective are generally considered lower-risk, whereas those without predicate devices sit higher on the risk scale. Additional considerations include quality assurance and risk mitigation activities.

Stage 5 (May 6, 2028)

“By year four, all other tests will need to be submitted to the FDA unless they are exempt or fall into enforcement discretion,” Bennett said. For LDTs with a predicate device, this likely means the 510(k) pathway; for those without, the De Novo pathway may be more appropriate.

Key considerations

Many LDTs may be exempt from some or all of the FDA’s new requirements. Bennett urged labs to familiarize themselves with the FDA’s database of exemptions for Class I and II medical devices² and the enforcement discretion policies included in the final rule (see Table 1 below).³

“The situation is still evolving,” Ballard added, pointing to examples such as the Congressional Review Act resolution to repeal the rule and the American Clinical Laboratory Association’s court challenge. Uncertainty is to be expected—but the good news is that labs currently offering LDTs can continue to do so as long as they comply with requirements. “A lot of the concern when the proposed rule came out was that patients were going to lose access to critical care. At least for the short term, that’s not the case.”

What labs should do next

Ballard’s first recommendation for affected labs is to read the rule in full. She also advised reviewing the two proposed guidance documents issued alongside it^4,5—both of which deal with emergent situations—and commenting if needed. Following this, her advice is to focus on three key action areas:

1. Inventory your lab’s test menu. How many of your tests are LDTs—and what category does each one fall into? “You may want to develop different requirements for different tests or take a more conservative approach and apply the stricter requirements across all your tests,” Ballard said. “It’s going to be different for each lab.”
2. Get everyone on board. “Train your lab staff on the new requirements. It’s really important to get all staff involved because it’s a huge change and everyone will need to participate to make it work.”
3. Consider budget. The rule will have significant budget implications, particularly in Stages 4 and 5 when premarket submissions are required. Ballard recommended hiring quality assurance and regulatory affairs personnel with medical device experience to simplify implementation of the new requirements or seeking training or assistance from consulting firms. Labs must also factor in registration and application fees, new software and equipment, and other expenses involved in preparing to submit to the FDA—costs that run into the hundreds of thousands.

“There are still a lot of unanswered questions,” Ballard acknowledged. “Be patient. Be flexible. As we think things through and come up with solutions, we’ll eventually get to a place where labs are in compliance and still be able to operate [effectively].”

References:

1. 21 CFR Part 809. Medical Devices; Laboratory Developed Tests. Federal Register. May 6, 2024. https://www.govinfo.gov/content/pkg/FR-2024-05-06/pdf/2024-08935.pdf.
2. U.S. Food & Drug Administration. Medical Device Exemptions 510(k) and GMP Requirements. June 17, 2024. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm.
3. B. Enforcement Discretion Policies. Federal Register. May 6, 2024. https://www.federalregister.gov/documents/2024/05/06/2024-08935/medical-devices-laboratory-developed-tests#h-28.
4. Enforcement Policy for Certain In Vitro Diagnostic Devices for Immediate Public Health Response in the Absence of a Declaration Under Section 564; Draft Guidance for Laboratory Manufacturers and Food and Drug Administration Staff; Availability. Federal Register. May 6, 2024. https://www.govinfo.gov/content/pkg/FR-2024-05-06/pdf/2024-08934.pdf.
5. Consideration of Enforcement Policies for Tests During a Section 564 Declared Emergency; Draft Guidance for Industry and Food and Drug Administration Staff; Availability. Federal Register. May 6, 2024. https://www.govinfo.gov/content/pkg/FR-2024-05-06/pdf/2024-08933.pdf.