FDA’s Draft Guidance: Phase Out of LDT Enforcement Discretion

by Alan Minsk and Laura Dona

Thin Lizzy famously declared in their 1976 track hit, “The Boys Are Back in Town.” The same is true almost 50 years later, as the U.S. Food and Drug Administration has announced its plan to phase out its general enforcement discretion approach of laboratory developed tests (LDTs) and bring the boys back for enforcement. On May 6, 2024, FDA published its Final Rule, clarifying that in vitro diagnostic products (IVDs) are medical devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act), including when the manufacturer of the IVD is a laboratory. As such, LDTs will no longer be under FDA’s previous enforcement discretion policy, with certain exceptions and subject to the phase-out policy.

Previously, FDA published a draft guidance document, “Laboratory Developed Tests: Small Entity Compliance Guide.” This article provides a brief summary of FDA’s previous enforcement approach and a high-level overview of the phase-out policy as provided in the draft guidance. We will not discuss the Final Rule in detail here, which is already the subject of litigation. 

LDTs background

Since 1976, FDA has chosen to exercise enforcement discretion over LDTs concerning requirements, such as establishment registration and product listing, medical device reporting to FDA, current good manufacturing practices (GMPs), and premarket review. IVDs are reagents, instruments, and systems intended for use in diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body. LDTs are IVDs that are intended for clinical use and are designed, manufactured, and used within a single clinical laboratory that meets certain laboratory requirements.

In the past, LDTs were mostly designed, manufactured, and used in small volumes by laboratories serving local communities and mostly interpreted by a single team of physicians and pathologists for a patient. These LDTs typically employed manual techniques in their development and usage. With innovation, LDTs now increasingly rely on high-tech instrumentation and software, and are often connected to IT infrastructure and laboratory information management systems. This creates substantial personal and national security risks regarding patient privacy. Recognizing the need for increased regulation in this new landscape, FDA announced a five-part, four-year phaseout policy of FDA’s general enforcement discretion. Compliance expectations and timelines are as follows for each stage:

Stage 1: Starting May 6, 2025
- Medical device reporting
- Reporting of corrections and removals
- Complaint files

Stage 2: Starting May 6, 2026
- Registration, listing, labeling, investigational use, and other applicable requirements that are not a part of stages 1,3,4, or 5

Stage 3: Starting May 6, 2027
- Quality system requirements not addressed in earlier stages

Stage 4: Starting Nov. 6, 2027
- Premarket submission requirements for high-risk IVDs offered as LDTs

Stage 5: Starting May 6, 2028
- Premarket submission requirements for low and moderate risk IVDs offered as LDTs, unless exempt

Scope

The four-year phaseout plan begins on May 6, 2025, but this policy does not encompass all LDTs, as described below. In the draft guidance, FDA provides further detail regarding its compliance expectations for certain categories of IVDs (Table 2). FDA intends to continue its enforcement discretion regarding different aspects of LDTs. It intends to continue the general enforcement discretion approach and generally not enforce any applicable requirements for the following categories of tests:

• 1976-Type LDTs

• Certain Human Leukocyte Antigen (“HLA”) Tests for Transplantation

• Forensic Tests

• Department of Defense (“DoD”) and Veterans Health Administration (“VHA”) LDTs

FDA generally intends to maintain enforcement discretion regarding premarket review requirements for LDTs approved by New York State Department of Health’s Clinical Laboratory Evaluation Program (CLEP), and modified versions of another manufacturer’s 510(k) cleared or de novo authorized test.

FDA generally intends to maintain enforcement discretion regarding premarket review and QSRs for LDTs for unmet needs, (i.e., LDTs manufactured and performed in laboratories integrated within a healthcare system to meet an unmet need of patients receiving care), and currently marketed IVDs offered as LDTs (e.g., IVDs first marketed prior to May 6, 2024, the date of the LDT Final Rule publication), and not modified after that date or only modified in limited ways. The agency also plans to exercise enforcement discretion for non-molecular antisera LDTs for rare red blood cell (RBC) antigens for transfusion compatibility.

The guidance document offers additional resources to help small firms comply with applicable FDA requirements regarding complaints, Medical Device Reports, and Correction and Removal Reports Requirements, Medical Device Reports of reportable events, Registration and Listing requirements, Device Labeling requirements, Investigational Use requirements, Quality System requirements, and premarket review requirement.

Practical tips and observations

FDA adopted its previous enforcement discretion policy with a different technological landscape in mind. The need to enforce standards of safety and efficacy grew with technological innovation. The phaseout policy is long-awaited, and FDA appears to have considered many of industry’s concerns regarding the implementation of the policy, as it was first announced will still exercise certain discretion where it views its past policy as consistent with its goals of ensuring safety and efficacy for the public health. 

The policy reflects the agency’s ongoing commitment to ensuring that the products it regulates are safe and effective for their intended use. As technology advances, FDA may shift its focus to products that it sees as offering more risk to the public health. We can expect that, as technology continues to advance, it will continue to evaluate its enforcement priorities. It looks like FDA is “back in town” with a new enforcement policy, but with the litigation, it is not clear how long it can stay. 

Firms affected by this change should become familiar with this phaseout policy, even if the compliance dates seem far away. Also, if a product is of a higher risk, companies should recognize that this development may bring about more attention from FDA. Understanding specific changes in regulatory responsibility under the phaseout policy allows firms to set workable timelines for compliance.

* Because these tests are LDTs, FDA generally will not expect compliance with the QSR requirements, except for design controls, purchasing controls, acceptance activities, corrective and preventative action (“CAPA”) activities, and records requirements. ** For tests that are LDTs, FDA generally will not expect compliance with the QSR requirements, except for design controls, purchasing controls, acceptance activities, CAPA activities, and records requirements.

About the authors: Alan Minsk is a partner and co-chair of the Food & Drug practice at Arnall Golden Gregory LLP. He can be reached at [email protected]. Laura Dona is an associate in the Food & Drug practice at Arnall Golden Gregory LLP. She can be reached at [email protected]. The authors would like to thank AGG summer associate Vanessa Okojie for her contributions to this Bulletin.

Footnotes

1. 89 Fed. Reg 37286.
2. 89 Fed. Reg 37286.
3. NYS CLEP seeks to ensure the accuracy and reliability of test results in clinical laboratories located in or accepting specimens from New York. For an LDT to meet CLEP standards, it is put through a more rigorous validation measure and review than other LDTs.
4. This discretion only applies to modifications following design controls and other quality system requirements (QSRs), and where the test is being performed in the laboratory making the modification. Premarket review submissions are expected when the change is significant such that it is no longer substantially equivalent to the original IVD, or where FDA would expect the original manufacturer to submit the change for premarket review.
5. This discretion only applies when such tests are manufactured and performed by blood establishments, including transfusion services and immunohematology labs, when no alternative IVD is available to meet the patient’s need for compatible blood transfusion. This discretion does not apply to genotyping RBC antigen molecular tests.
6. FDA does not explain what “generally” means for the purposes of this enforcement guidance, but we understand that the agency’s continued discretion is based on its determination that these device-types are unlikely to pose significant risks or are conducted in circumstances that themselves will mitigate the risks. This use of “generally” provides FDA flexibility to step in, if it determines that there is a higher-than-expected risk in a given circumstance.