On April 29, 2024, the Food and Drug Administration (FDA) announced a final rule to consider laboratory-developed tests (LDTs) to be medical devices and thus under FDA oversight.1 LDTs are laboratory tests that are designed, manufactured, and used within a single clinical laboratory, often in academic medical centers or research hospitals. LDTs are typically made to address very specific needs, such as testing for rare diseases, and are manufactured in small volumes as opposed to commercially manufactured and marketed laboratory tests. In the past, LDTs fell under the Clinical Laboratory Improvement Amendments (CLIA) which is overseen by the Centers for Medicare and Medicaid Services (CMS) rather than the FDA.
The old regulatory framework allowed clinical laboratories with CLIA accreditation to develop and perform their own tests to fill gaps in available testing. As the type of LDTs evolved and their use increased, the FDA became concerned that LDTs may be unreliable and could result in inappropriate clinical care.2 As a result, the FDA determined that more oversight was necessary. Since the FDA believes LDTs are an in vitro diagnostic (IVD) product intended for clinical use, the agency wants LDTs to fall under its regulations for medical devices.
The final rule, published on May 6, 2024, will phase in this oversight over a four-year period, with LDTs currently on the market grandfathered into approval.3In the announcement of the final rule, FDA Commissioner Robert Califf, M.D. stated, "The final rule announced today aims to provide crucial oversight of these tests to help ensure that important healthcare decisions are made based on test results that patients and healthcare providers can trust."4 The Centers for Medicare and Medicaid Services (CMS) agrees with the FDA, and the agencies released a joint statement on January 18, 2024, to address the need for oversight, stating, "Both CMS and the FDA believe that patients and their doctors need to know that LDTs are valid."5
The American Clinical Laboratory Association (ACLA) and the American Hospital Association (AHA) have criticized the new rule, expressing concerns that the rule will limit patient access to LDTs that could be important to their clinical care. The ACLA and one of its member laboratories, HealthTrackRx, filed a lawsuit against the FDA on May 29, 2024, to challenge this final rule, saying that "Congress has never granted FDA authority to regulate the professional testing services that laboratories provide..."6
Under the final rule, LDTs will be required to follow FDA regulations for IVD products for human use as spelled out in 21 Code of Federal Regulation (CFR) Part 809. However, since the FDA has had a general enforcement discretion approach to LDTs in the past, the FDA will phase out that approach, and phase in their oversight, over a four-year period. The final rule spells out five stages of the phase-out of the general enforcement discretion approach, which is summarized as follows:
Stage 1 - One year after the publication date of the final rule, FDA will expect compliance with the medical device report (MDR) requirements, correction and removal reporting requirements, and quality system (QS) requirements under 21 CFR 820.198.
Stage 2 - Two years after the publication date of this final rule, FDA will expect compliance with registration and listing requirements, labeling requirements, and investigational use requirements.
Stage 3 - Three years after the publication date of this final rule, FDA will expect compliance with QS requirements under 21 CFR part 820 (other than requirements under § 820.198 already addressed in stage 1).
Stage 4 - Three years and six months after the publication date of this final rule, FDA will expect compliance with premarket review requirements for high-risk IVDs offered as LDTs (IVDs that may be classified into class III or that are subject to licensure under section 351 of the Public Health Service Act) unless a premarket submission has been received by the beginning of this stage in which case FDA intends to continue to exercise enforcement discretion for the pendency of its review.
Stage 5 - Four years after the publication date of this final rule, FDA will expect compliance with premarket review requirements for moderate-risk and low-risk IVDs offered as LDTs (that require premarket submissions), unless a premarket submission has been received by the beginning of this stage in which case FDA intends to continue to exercise enforcement discretion for the pendency of its review.
What does this mean for laboratories making LDTs? After the phase-out period, the FDA will expect laboratories manufacturing and offering LDTs to comply with the regulations applicable to devices such as establishment registration, product listing, labeling standards, adverse event reporting, investigational controls including classification of the LDT as significant risk or non-significant risk, and submission of an investigational device exemption (IDE) before beginning a study of a significant risk LDT. The laboratories will also be subject to inspections by the FDA and the LDTs will be subject to premarket review by the FDA.
As academic medical centers and research hospitals are well aware, compliance with FDA regulations can be complicated, time-consuming, and costly. The protection of human subjects participating in clinical trials of FDA-regulated drugs, devices, or biologics is worth the time, effort, and expense. The FDA argues that those same protections should be extended to patients who may receive an LDT as part of their clinical care or who may participate in a research study of the LDT.
The ACLA disagrees. "Laboratory developed testing services are not medical devices and subjecting them to medical device regulation will harm patient access to needed testing and compromise innovations that drive personalized medicine...The rule will limit access to scores of critical tests, increase healthcare costs, and undermine innovation in new diagnostics," stated Susan Van Meter, president of the ACLA, upon the announcement of the Final Rule.7
In response to a request for information on the FDA's proposed rule, AHA submitted a letter to Senate Health, Education, Labor & Pensions Committee Ranking Member Bill Cassidy, M.D. (R-LA), that stated, "While we support the need for additional oversight of the development and use of some LDTs and in-vitro diagnostics (IVDs) offered as LDTs, the FDA's proposal to apply its device regulations to hospital and health system LDTs is misguided. These tests are not devices — they are diagnostic tools developed and used for essential patient care. Regulating LDTs under the FDA's device regulatory framework could cause patients to lose access to many critical tests and stifle innovative advances in hospital and health system laboratory medicine."8
After the announcement of the Final Rule, AHA executive vice president Stacey Hughes said, "We remain concerned that many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork, especially as certain FDA device requirements are phased in over the next four years. As a result, this will cause a substantial reduction in patient access to innovative and targeted diagnostic tests. We will continue to evaluate the rule closely and work with the FDA."9
While it remains to be seen whether the Final Rule will stand or be amended following the ACLA's lawsuit, laboratories that design and manufacture LDTs should be prepared to begin the phase-out of the general enforcement discretion approach by familiarizing themselves with the FDA device regulations that may become effective for LDTs. If the Final Rule stands, laboratories will likely need to add regulatory staff to ensure compliance with the regulations. Patients should be aware that the LDTs they once relied on or hoped to rely on may become less available as laboratories scramble to implement new processes and procedures to meet the FDA's requirements.
Footnotes
1. Food and Drug Administration, "FDA Takes Action Aimed at Helping to Ensure the Safety and Effectiveness of Laboratory Developed Tests" (April 29, 2024),
2. Rachel Roubein and Daniel Gilbert, "FDA moves to regulate some tests it says may be unreliable" The Washington Post (April 29, 2024)
https://www.washingtonpost.com/health/2024/04/29/fda-lab-developed-test-medical/
3. Food and Drug Administration, "Medical Devices: Laboratory Developed Tests" 89 FR 37286 (May 6, 2024)
4. Food and Drug Administration, "FDA Takes Action Aimed at Helping to Ensure the Safety and Effectiveness of Laboratory Developed Tests" (April 29, 2024),
5. Food and Drug Administration, "FDA and CMS: Americans Deserve Accurate and Reliable Diagnostic Tests, Wherever They Are Made" (January 18, 2024),
6. American Clinical Laboratory Association, "ACLA Challenges FDA's Final Rule To Regulate Laboratory Developed Testing Services As Medical Devices" (May 29, 2024)
7. American Clinical Laboratory Association, "ACLA Statement On FDA Final Rule To Regulate Laboratory Developed Testing Services As Medical Devices" (April 29, 2024)
8. American Hospital Association, "AHA to Congress: FDA proposed rule for laboratory developed tests overreaches" (April 1, 2024)
9. American Hospital Association, "FDA issues final rule applying medical device rules to laboratory developed tests" (April 29, 2024)
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