What does the FDA’s final rule on laboratory-developed tests (LDTs) change?

The rule makes it explicit that in vitro diagnostics (IVDs) that are manufactured by clinical laboratories—i.e., laboratory-developed tests (LDTs)—are considered devices under the Federal Food, Drug, and Cosmetic Act (FDCA). IVDs are tests performed on samples such as blood or tissue that have been taken from the human body. LDTs are designed and used within a single laboratory that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).

In the final rule, rather than creating a definition of LDTs, the FDA added 10 words to the regulatory definition for IVD products.

In vitro diagnostic products are those reagents, instruments, and systems intended for use in the 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. These products are devices as defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (the act), and may also be biological products subject to section 351 of the Public Health Service Act, including when the manufacturer of these products is a laboratory.

When will the changes take effect?

The rule was published in the Federal Register on May 6, 2024. The FDA established a four-year, five-stage “phaseout policy” during which medical device law is phased in for LDTs.

Key Dates:

Stage 1—May 6, 2025
Stage 2—May 6, 2026
Stage 3—May 6, 2027
Stage 4—November 6, 2027
Stage 5—May 6, 2028

timeline

What are the policies?

The FDA will phase out its general enforcement discretion approach for LDTs so that IVDs “manufactured” by a laboratory will generally fall under the same enforcement approach as other IVDs. The FDA is adopting targeted enforcement discretion policies for specific categories of IVDs manufactured by a laboratory.

Which categories of IVDs remain under the targeted enforcement discretion policy?

  • “1976-type” LDTs, which have the following characteristics:
    • Use manual techniques (without automation and without the use of software) that are performed by laboratory personnel with specialized expertise
    • Use components legally marketed for clinical use
    • Are designed, manufactured, and used within a single CLIA-certified laboratory that meets the requirements under CLIA for high-complexity testing
      • Examples of 1976-type IVDs include certain immunohistochemistry tests, cystic fibrosis sweat tests, certain colorimetric newborn screening tests, karyotypic tests.
  • Human leukocyte antigen (HLA) tests for transplant, which have the following characteristics:
    • Are designed, manufactured, and used within a single CLIA-certified laboratory that meets the requirements under CLIA for high-complexity histocompatibility testing when used in connection with organ, stem cell, and tissue transplantation to perform HLA allele typing for HLA antibody screening and monitoring, or for conducting real and “virtual” HLA cross-match tests
  • Forensic tests
    • Tests intended solely for law enforcement
  • Department of Defense (DoD) or Veterans Health Administration (VHA) tests
  • Public health surveillance tests

Which other tests are subject to enforcement discretion?

  • Currently marketed LDTs: LDTs that were marketed before May 6, 2024, that are not modified, or that are modified in certain limited ways
  • New York State Clinical Laboratory Evaluation Program (NY CLEP)-approved LDTs: LDTs approved by the NY CLEP will generally not be subject to premarket review requirements.
  • “Unmet needs” LDTs: LDTs manufactured and performed by a laboratory integrated within a healthcare system to meet an unmet need for patients within the same healthcare facility
    • The FDA does not consider this to include patients who are being treated at an affiliated hospital with a different corporate ownership than the laboratory.
    • “Unmet need” means that there is no available FDA-authorized IVD that meets the patient’s needs. Example scenarios include rare diseases, or when the FDA-authorized IVD is not indicated for use on the patient, or when the FDA-authorized IVD is not available to the patient.

Were some tests grandfathered?

Not completely. For example, currently marketed LDTs are subject to listing and labeling requirements within two years, and monitoring going forward. Although currently marketed LDTs are not required to be submitted to the FDA for review and approval, the listing and labeling requirements will still mean a significant amount of work for many clinical laboratories.

ARUP Laboratories hosted a webinar for clients, members of the media, and others on May 23, 2024. Jonathan Genzen, MD, PhD, chief medical officer and senior director of governmental affairs, and Jonathan Carr, JD, chief compliance officer, summarized the details of the final rule and discussed the anticipated challenges for labs, patients, and providers. Register here.