On May 6, 2024, the U.S. Food and Drug Administration (FDA) issued its final rule significantly modifying FDA's approach to oversight of laboratory developed tests (LDTs). The final rule is effective July 5, 2024.
The final rule amends FDA's regulations to clarify that in vitro diagnostic products (IVDs) are devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act) including when the manufacturer of the IVD is a laboratory. In addition to this amendment, FDA is finalizing its policy under which FDA will increase oversight of LDTs, a subset of IVDs, through a phased implementation of IVD requirements. This phased implementation will take place over the course of four years.
What are LDTs?
LDTs are intended to measure or detect substances or analytes (e.g., proteins, glucose, cholesterol, or DNA) in specimens taken from humans (e.g., blood, saliva, or tissue). LDTs are intended to be designed, manufactured, and used within a single laboratory that meets certain Clinical Laboratory Improvement Act (CLIA) requirements.
LDT Regulatory Approach Since 1976
FDA has long asserted its authority to regulate LDTs as devices but previously had deemed the products low risk and, therefore, opted to take a broad enforcement discretion approach to regulating these products. Under its enforcement discretion approach, FDA has not enforced certain device requirements, such as premarket review, reporting, registration and listing, quality system, etc.
FDA had historically viewed LDTs as low-risk because they were typically manufactured in small volumes in local communities for rare diseases, using low-tech instruments and specialized personnel. LDTs have become significantly more complex since 1976. Currently, many laboratories manufacturing LDTs employ high-tech instruments (such as algorithms and automation), run the LDTs in high volumes, and widely market and accept specimens from across the United States.
Both FDA and Congress have previously pursued changes to FDA's enforcement discretion policy several times. FDA has previously attempted to modify its approach through guidance, which was never finalized, and members of Congress have introduced but failed to pass new legislation, most recently, the Verifying Accurate, Leading-edge IVCT Development Act (VALID Act).
Final Rule — FDA's Phaseout of Enforcement Discretion
FDA issued its proposed rule in October 2023. The proposed rule proposed a phased approach to ending enforcement discretion. The proposed rule included several categories of tests that would continue to benefit from limited enforcement discretion. The final rule substantially mirrors the proposed rule but includes some additional categories of tests that will continue receiving enforcement discretion.
At a high level, the Phased Implementation of IVD requirements will be as follows:
| Stage | Action |
| Stage 1 (May 6, 2025) | FDA will expect compliance with medical device reporting (MDR) requirements, correction and removal reporting requirements, and quality system (QS) requirements regarding complaint files. |
| Stage 2 (May 6, 2026) | FDA will expect compliance with requirements not covered during other stages of the phaseout policy, including registration and listing requirements, labeling requirements, and investigational use requirements. |
| Stage 3 (May 6, 2027) | FDA will expect compliance with QS requirements. |
| Stage 4 (November 6, 2027) | FDA will expect compliance with premarket review requirements for high-risk 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 (May 6, 2028) | FDA will expect compliance with premarket review requirements for moderate-risk and low-risk 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. |
FDA will continue exercising certain levels of enforcement discretion over several LDTs, as described below. The final rule contains key criteria each test must meet to avail itself of the enforcement discretion.
Full Enforcement Discretion:
- "1976-type" LDTs (i.e., LDTs using manual techniques and legally marketed components)
- Certain Human Leukocyte Antigen Tests for Transplantation
- Forensic (Law Enforcement) Tests
- Public Health Surveillance Tests
- Department of Defense or Veterans Health Administration Performed Tests
Limited Enforcement Discretion:
- Nonmolecular Antisera LDTs for Rare Red Blood Cell Antigens
- Modifications by a Laboratory of Another Manufacturer's 510(k) Cleared or De Novo Authorized Test (if modification would not otherwise constitute a modification requiring a submission and is within scope described in preamble)
- LDTs approved by the New York State Department of Health Clinical Laboratory Evaluation Program (NYS CLEP)
- LDTs Marketed Prior to Issuance of Final Rule (May 6, 2024) (and not modified beyond scope described in preamble)
- LDTs for Unmet Needs by Labs Integrated in the Health Care System Treating the Patient
No Enforcement Discretion:
- IVDs Offered as LDTs Within Scope of Phaseout Policy (but that do not fall within a targeted enforcement discretion policy)
- Direct-to-Consumer (DTC) Tests (compliance currently expected)
- Donor Screening Tests for Infectious Diseases and Certain Blood Typing Tests (compliance currently expected)
Potential Challenges
It is likely that this final rule will be challenged in court. FDA received over 6,500 comments on the proposed rule, many of which challenge FDA's authority to regulate LDTs. Comments touched on a number of topics such as whether Congress granted FDA authority to regulate LDTs or whether the enactment of CLIA illustrates that authority to regulate LDTs lies with the Centers for Medicare & Medicaid Services (CMS); whether LDTs are "medical devices" under the FD&C Act; whether FDA may regulate LDTs because FDA cannot regulate the practice of medicine (which may include laboratory testing activities); whether the 60-day comment period was insufficient to give the industry time to respond; and whether the rulemaking implicates the "major questions doctrine." If challenged in court, we may see the issuance of a preliminary injunction.
The final rule may spur Congress to act. The new final rule has vocal opponents in Congress and may prompt members of Congress to reinvigorate the VALID Act or similar legislation and such legislation, if passed, could override FDA's efforts. The VALID Act currently contains language that places LDTs and IVDs under a single diagnostic regulatory scheme called "in vitro clinical tests (IVCTs)." The legislation would clarify the authority between FDA and CMS and settle the debate of how LDTs should be regulated.
Next Steps
Manufacturers should begin preparing themselves for compliance with requirements per the phased policy articulated above and watch out for any new FDA guidance intended to complement the final rule. In case of potential challenges, we recommend that stakeholders stay up to date with legal, legislative, and regulatory action on this issue.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.