On April 29, 2024, the Food and Drug Administration (FDA) filed a final rule (link) that explicitly labels laboratory developed tests (LDTs) as devices, subjecting them to the same FDA enforcement approach as all other in vitro diagnostics (IVDs) under the Federal Food, Drug, and Cosmetic Act (FD&C Act). The final rule is scheduled to be published in the Federal Register on May 6, 2024; it becomes effective 60 days after the date of publication.

Previously, the FDA exercised enforcement discretion for most LDTs. Given the increasing complexity and widespread use of LDTs, among other factors, the FDA no longer believed enforcement discretion was appropriate. Thus, the FDA is ending its general enforcement discretion approach for LDTs via a phaseout policy over the next four years. The FDA will maintain targeted enforcement discretion policies for specific categories of IVDs, including currently marketed IVDs offered as LDTs and LDTs performed by a laboratory integrated within a healthcare system to meet an unmet need.

LDT Phaseout Policy

The Phaseout Policy will occur over a 4-year period and across 5 different stages. The phaseout will apply to IVDs manufactured and offered as LDTs by laboratories that are certified under the Clinical Laboratory Improvement Amendments (CLIA) program.

Stage 1 (1 year after publication of final rule): Medical device reporting (MDR) requirements, correction and removal reporting requirements, and quality system (QS) requirements under§ 820.198 (21 CFR 820.198)
Stage 2 (2 years after publication of final rule): Other requirements not otherwise listed including registration and listing requirements, labeling requirements, and investigational use requirements  
Stage 3 (3 years after publication of final rule): QS requirements under 21 CFR part 820 (other than requirements under § 820.198)
Stage 4 (3.5 years after publication of final rule): Premarket review requirements for high-risk IVDs (e.g., classified as class III devices)
Stage 5 (4 years after publication of final rule): Premarket review requirements for moderate risk and low risk IVDs offered as LDTs

FDA Response to Public Comments

The comment period for the proposed rulemaking opened on October 3, 2023, and closed on December 4, 2023. During this time, the FDA received more than 6,500 comments from stakeholders across medical device associations, pharmaceutical industries, professional associations, hospitals and academic medical centers (AMCs), advocacy organizations, government agencies, and more. Highlights of FDA’s response to comments by topic include:

General Comments on the Notice of Proposed Rulemaking: FDA takes the stance that phasing out general enforcement discretion for LDTs will help ensure oversight and effectiveness and disagrees with comments stating that the ruling is overly broad, difficult to follow, and that the FDA is “unfit for the purpose of assessing the quality.”
Need for a Rule: FDA addressed numerous comments stemming from the contested need for an FDA rule on LDT regulation.
The FDA disagrees with claims that patient risk is unchanged from 1976 and that all clinicians are “well aware” of test limitations and implications given high-stakes medical decisions across many diseases and conditions reliant on LDT results. Namely, genetic sequencing technologies which have significantly advanced and are aware of offerings that lack sufficient scientific support.
The FDA agrees with comments that CLIA and CLIA regulations are not a substitute for FDA’s oversight of IVDs offered as LDTs under the FD&C Act. FDA believes that CLIA does not provide sufficient assurance of safety and effectiveness but instead establishes requirements for laboratory operations. CMS agrees that their role is distinctly separate yet complimentary to the role of FDA and cites the lack of resources and expertise within CMS to “modernize” CLIA.
FDA disagrees with comments claiming that there is no problem with LDTs or that deficiencies in laboratory testing are mostly caused by operational or human error. FDA has exposed evidence of problems and provided written support.
All relevant components of HHS, including CMS, NIH, and HHS leadership, reviewed and cleared FDA’s proposed and final rule.
Phaseout Policy: FDA considered comments received and made various changes to the phaseout policy. FDA intends to exercise enforcement discretion for:
1976-Type LDTs
 Human Leukocyte Antigen (HLA) tests  
Tests for forensic usage
LDTs manufactured and performed within the Veterans Health Administration (VHA) or the Department of Defense (DoD)
LDTs approved by New York State Department of Health Clinical Laboratory Evaluation Program (NYS CLEP)
LDTs manufactured and performed by a laboratory integrated with a healthcare system to meet an unmet need of patients receiving care within the same healthcare system
Currently marketed IVDs offered as LDTs that were first marketed prior to the date of issuance of the final rule and that are not modified, or that are modified in certain limited ways
Non-molecular antisera LDTs for rare red blood cell (RBC) antigens where such tests are manufactured and performed in blood establishments, including transfusion services and immunohematology laboratories and where there is no alternative available to meet the patient’s need for a compatible blood transfusion.
Additionally, IVDs that fall outside the scope of the Phaseout Policy include:
Tests that are intended as blood donor screening or human cells, tissues and cellular and tissue-based products (HCT/P) donor screening tests required for infectious disease testing
Tests intended for emergencies, potential emergencies, or material threats
Tests intended for consumer use (without meaningful involvement by a licensed healthcare professional)
FDA Authority to Regulate LDTs: FDA states that LDTs, like other IVDs, are “devices” subject to applicable requirements in the FD&C Act. FDA disagrees that its enforcement discretion approach suggests that FDA lacks or “waived” authority over LDTs.
Impact on Innovation, Access and Small Businesses: FDA anticipates that enforcement discretion policies will sufficiently address financial and administrative challenges for smaller laboratories. FDA has made several changes to the phaseout policy, including the addition of certain enforcement discretion policies which significantly reduce the economic impact of the phaseout policy, and thus the likelihood that laboratories may reduce their test offerings or exit the market.

Notable Changes in Final vs. Proposed Rule

Academic Medical Centers – While not a wholesale carve-out for academic medical centers, the FDA is including an enforcement discretion policy (with respect to premarket review and most QS requirements) for LDTs manufactured and performed by a laboratory integrated within a healthcare system to meet an unmet need of patients receiving care within the same healthcare system.
Existing LDTs – FDA will exercise enforcement discretion (with respect to premarket review and most QS requirements) for IVDs offered as LDTs that were marketed on the date of issuance of the final rule as long as they are not modified (or are modified but only in a limited way).
Modifications to LDTs – FDA will exercise enforcement discretion (with respect to premarket review and most QS requirements) for modifications to currently marketed IVDs (first marketed prior to the date of issuance of the final rule) offered as LDTs that do not:
change the indications for use of the IVD;
alter the operating principle of the IVD (e.g., changes in critical reaction components);
include significantly different technology in the IVD; or
adversely change the performance or safety specifications of the IVD.
LDTs Approved by New York State Department of Health Clinical Laboratory Evaluation Program (NYS CLEP) – FDA will exercise enforcement discretion (with respect to premarket review requirements) for high risk and moderate risk LDTs approved by NYS CLEP. Generally, FDA believes that NYS CLEP’s review of analytical and clinical validity of LDTs helps to mitigate the risk of harm from inaccurate and unreliable LDTs.

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