The LDT final rule intends to improve patient safety by ensuring LDTs meet the same standards as other medical devices. The rule also provides wider exemptions than previously anticipated for LDTs already on the market. It includes a phased, five-stage “phase-out” of enforcement discretion over four years, demanding escalating compliance from labs, with certain exemptions for tests addressing “unmet needs” and those approved by specific programs. The FDA’s final rule on laboratory-developed tests (LDTs) introduced a significant regulatory shift. It will now regulate these tests as well as other medical devices and in vitro diagnostics. The rule offers wider exemptions than previously anticipated for LDTs on the market by May 6th and tests approved by the New York State Department of Health’s Clinical Laboratory Evaluation Program. Notably, it does not offer specific carve-outs for academic medical centers, except for a general exemption for tests addressing “unmet needs.”
The schedule for the FDA’s Laboratory Developed Tests (LDT) final rule:
April 29, 2024: The FDA announced the final rule that LDTs will be regulated as medical devices.
May 6, 2024: The rule was published in the Federal Register.
60 days after publication: The rule went into effect, on July 5, 2024.
May 6, 2025: The first compliance date for the FDA’s phase-out of its enforcement discretion policy for LDTs.
Final Rule Contents:
The recently released pre-publication version of the FDA’s LDT Final Rule represents a significant shift in the regulatory landscape for LDTs. The 528-page document enacts a singular yet pivotal amendment to the codified regulations concerning in vitro diagnostic products. Specifically, the rule modifies the definition at 21 C.F.R. § 809.3(a) to explicitly include laboratory-produced tests under the umbrella of “devices” as defined by section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (FDCA). This adjustment ensures that all LDTs are recognized as “devices,” thereby subjecting them to FDA’s regulatory authority. This new rule is a shift from discretionary enforcement to a more definitive regulatory posture, applying not only to traditional LDTs designed, manufactured, and used within a single laboratory but also extending to all tests developed by laboratories, even those that might not fit the traditional LDT definition. The FDA is setting a clear regulatory framework encompassing all laboratory-developed in vitro diagnostics, irrespective of their specific characteristics or the context of their use.
Phase-Out of Enforcement Discretion:
The FDA has outlined a structured “phase-out” policy for its enforcement discretion for LDTs, transitioning towards full regulatory oversight. This gradual shift, scheduled over a four-year period, is structured into five distinct stages, each imposing increasingly stringent requirements. The FDA’s intention behind this phased approach is to ensure a manageable transition for laboratories to comply with the statutory and regulatory device premarket and post market requirements.
Stage 1
Starting one year after the publication of the LDT Final Rule, the FDA will require laboratories to comply with Medical Device Reporting (MDR) requirements under 21 C.F.R. Part 803, correction and removal reporting requirements under 21 C.F.R. Part 806, and complaint handling requirements under 21 C.F.R. § 820.198. Notably, the final rule has shifted the requirement for complaint handling from Stage 3 (as initially proposed) to Stage 1, emphasizing its importance for effective MDR compliance.
Stage 2
Two years post-publication, laboratories must adhere to additional regulatory requirements not covered in other stages, including registration and listing under 21 C.F.R. Parts 607 and 807, labeling requirements under 21 C.F.R. Parts 801 and 809, and investigational use requirements under 21 C.F.R. Part 812. This stage now explicitly includes investigational use requirements, addressing past confusion and non-compliance in this area as recognized by the FDA.
Stage 3
Three years after the rule’s publication, compliance with 21 C.F.R. Part 820 is expected, except for complaint handling requirements, which are moved to Stage 1 from the original proposed rule. By the effective date of this stage, the Quality System Regulation (QSR) will transition to the revised Quality Management System Regulation (QMSR), effective from February 2, 2026. The FDA also notes the expectation for laboratories to retain relevant manufacturing records created before this stage, particularly those pertinent to validation and other topics under recordkeeping requirements in 21 C.F.R. Part 820, Subpart M.
Stage 4
At 3.5 years after publication, the FDA expects laboratories to meet premarket review requirements for high-risk IVDs classified as Class III devices. Laboratories that submit a premarket review by the beginning of this stage will continue to benefit from the FDA’s enforcement discretion during the review process. This stage remains unchanged from the proposal.
Stage 5
Four years following publication, the FDA will enforce compliance with premarket review requirements for moderate-risk and low-risk IVDs that are non-510(k)-exempt Class I and II devices. Like Stage 4, if a premarket submission is made by the onset of this stage, the FDA will maintain its enforcement discretion during the review period. This final stage also remains consistent with the proposed rule.
Carve-Outs:
Carve-outs are detailed in the preamble to the LDT Final Rule. These carve-outs indicate areas where the FDA will continue to exercise enforcement discretion by not applying certain statutory requirements. However, the preamble notes that the FDA can modify these exceptions at its discretion. This creates a degree of regulatory uncertainty, reflecting the challenges in transitioning all LDTs to full regulatory oversight. The FDA plans to enhance the Third Party 510(k) review program to handle about 50% of reviews for low- and moderate-risk LDTs and to adjust Medical Device User Fee Amendments (MDUFA) during its next reauthorization to cover IVD and LDT premarket submissions.
Significant carve-outs:
Currently marketed LDTs: The FDA will not enforce premarket review and Quality System Regulation compliance (except for recordkeeping requirements under 21 C.F.R. Part 820, Subpart M) for LDTs that were marketed before the issuance of the LDT Final Rule. However, these LDTs must still meet Medical Device Reporting requirements, correction and removal reports, registration and listing, and labeling requirements. This exemption aims to allow currently marketed tests to continue without the burden of the most stringent new requirements.
Modifications to existing LDTs: If an existing LDT undergoes significant modifications affecting its use, technology, or performance, the FDA will require premarket review and QSR compliance for the altered test.
Tests meeting unmet needs: Tests developed within a healthcare system to address unmet patient needs where no FDA-approved alternative exists. The FDA has acknowledged over 100 comments on this point and plans to issue further guidance on this policy.
Non-molecular Antisera LDTs: For rare red blood cell antigens, these tests are exempt when performed by blood establishments with no alternative IVD available.
New York State Clinical Laboratory Evaluation Program (CLEP)L LDTs approved by NYS CLEP for moderate-risk and high-risk are considered to have passed sufficient review to substitute for FDA premarket review, though they are still subject to post market requirements.
Continued Enforcement discretion:
“1976-Type LDTs”: These tests resemble those available in 1976 and involve manual techniques, legally marketed components, and are performed in a single CLIA-certified laboratory.
Human leukocyte antigen tests: Used for organ, stem cell, and tissue transplantation within a single CLIA-certified lab.
Forensic tests: Designed solely for law enforcement purposes.
Non-molecular Antisera LDTs : For rare red blood cell antigens, these tests are exempt when performed by blood establishments with no alternative IVD available.
Tests within the Department of Defense or Veterans Health Administration: Manufactured and performed within these entities.
Controversy:
Some companies have legally challenged the FDA about the final rule, and the issue is expected to return to the legislative arena with the Presidential election results being a factor. Previous efforts by Congress to explicitly regulate LDTs, such as the Verifying Accurate, Leading-edge IVCT Development (VALID) Act, have failed to pass. The concessions and carve-outs included in the FDA’s LDT Final Rule, which were necessary for the FDA to maintain a practical regulatory authority over laboratories, will serve as a baseline for any legislative efforts. These elements reflect the complex interplay between regulatory intent, industry capability, and legislative action in the ongoing governance of LDTs.
Timeline to prepare for the end of LDT Enforcement Discretion:
Preparations for the end of LDT enforcement discretion should include a regulatory gap assessment and strategic planning, QMS Development and compliance framework setup, submission and registration of all required FDA documentation, implementation of comprehensive training programs, and ongoing regulatory updates to ensure sustained compliance. Specifically, Premarket Approval for High-risk LDTs (3.5 Years Post-Publication)-Premarket Submission Planning (Start by 30 Months): Begin gathering necessary data and preparing premarket approval applications for high-risk LDTs, ensuring submission by the start of Stage 4.Premarket Notification for Low and Moderate-risk LDTs (4 Years Post-Publication)- Preparation for 510(k) Notification (Start by 36 Months): Prepare and submit 510(k) premarket notifications for low and moderate-risk LDTs.