Industry Focus: FDA Final Guidance for Laboratory Developed Tests

FDA Issues Small Entity Compliance Guide

When they originated in 1976, laboratory developed tests (LDTs) were manufactured and used locally for unique or regional pathologies.  Today, many LDTs are run in diverse populations and batched in high volumes outside of the patient healthcare setting, are used in multiple laboratories, and are really mislabeled in vitro diagnostic products (IVDs).  FDA has expressed additional concern that modern LDT’s are dependent on software, thereby creating a potential cybersecurity threat.  These concerns led to the LDT Final Rule entitled, “Medical Devices; Laboratory Developed Tests” (89 FR 37286) in which all IVDs are now classified as medical devices that are under the authority of the Federal Food, Drug, and Cosmetic Act (FD&C Act), regardless of where they are manufactured.  

On 6 May 2025, the FDA will begin a 4-year phase out period of its general enforcement discretion approach for LDTs.  The end goal is that all diagnostic products and tests within specific categories will be regulated under targeted enforcement discretion policies.  This phase out policy applies to IVDs offered and manufactured as LDTs by laboratories, which are Clinical Laboratory Improvement Amendment of 1988 (CLIA) certified and are able to perform high complexity testing according to the CLIA regulatory requirements.  

There are exceptions to the phase out policy including some emergency tests, direct to consumer tests, blood and tissue donor screening tests, and public health surveillance tests.  Additionally, FDA will most likely continue the general enforcement approach without applicable requirements on the following tests: 1976 Type LDTs, certain HLA test for transplantation, forensic test, and department of defense and veteran health administration LDTs.  

Concerning premarket review requirements, FDA intends to exercise enforcement discretion for LDTs approved by the New York State Department of Health’s Clinical Laboratory Evaluation Program, and some modified versions of other manufacturers De Novo authorized or 510(k) cleared tests.  The FDA will exercise enforcement discretion and will usually not enforce quality system requirements and premarket review beyond those discussed in 21 CFR part 820 for LDTs for unmet needs, IVDs that were first marketed prior to 6 May 2024, and non-molecular antisera LDTs for rare RBC antigens for transfusion compatibility.

The LDT guidelines for small entities and the 4-year phase out plan are further detailed in the “Laboratory Developed Tests: Small Entity Compliance Guide” which was published on 25 June 2024.  All of the enforcement discretion policies detailed in the small entity compliance guide are also discussed in the preamble to the LDT Final Rule. It is important to note that the new regulation and phaseout policy do not change the requirements for laboratories.

If you need assistance with your LDT to ensure you are complying with the new LDT rule, contact Facet today!