A Timeline of Laboratory-Developed Test Regulation in the US

The century-long history of the U.S. FDA’s relationship with LDTs

Michael Schubert, PhD

Michael Schubert, PhD, is a veteran science and medicine communicator. He holds graduate degrees in biochemistry and molecular biology with a research focus on chromatin structure and function and has written on subjects from subspeciality pathology to fictional science. In addition to writing and editing, he is co-director of the Digital Communications Fellowship in Pathology and professor of professional practice in academic writing at ThinkSpace Education, the University of Chichester.

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Published:May 23, 2024
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On April 29, the FDA announced a final rule amending its regulations explicitly stating that in vitro diagnostics (IVDs), including lab-developed tests or LDTs, are devices under the Federal Food, Drug, and Cosmetic Act. Here's a brief history of LDT regulation in the US.

A SNAPSHOT OF LAB-DEVELOPED TEST REGULATIONS
2003Amendments to CLIA ’88 introduce new requirements for LDTs but deem them outside the FDA’s purview.
2014The FDA releases draft guidance declaring that LDTs should be held to the same standards as IVDs.
2016The House Committee on Appropriations directs the FDA to suspend efforts to regulate LDTs.
2020The VALID Act is introduced in Congress outlining the FDA’s intent to regulate all in vitro clinical tests, including LDTs, but it is never passed.
2023The FDA announces proposed rule to regulate all IVDs and phase out its discretionary approach to LDTs.
2024

The FDA publishes final rule on LDTs and two draft guidance documents: enforcement discretion in declared emergency situations and in the absence of a declared emergency.
FDA LDT PHASEOUT DEADLINES
2025 Stage 1: Requires LDTs to comply with medical device reporting requirements, including correction and removal of tests, and quality system requirements regarding complaint files.
2026 Stage 2: Implementation of other IVD requirements not covered in Stage 3, e.g., registration.
2027 Stage 3 (May): Compliance with quality system requirements other than for complaints. 
Stage 4 (November): Premarket review requirements for high-risk LDTs, unless a premarket submission has been received.
2028 Stage 5: Expands premarket review requirement compliance to low- and moderate-risk LDTs for which a premarket submission has not been received.

For decades, the U.S. Food and Drug Administration (FDA) has asserted its authority over laboratory-developed tests (LDTs)—and for decades, professional bodies have pushed back against this authority, highlighting the importance of such tests to patient care and the need for their development to be within the reach of the clinical lab. 

With LDTs being regulated in the same way as commercially manufactured and marketed diagnostics, many labs lack the resources to comply, limiting their ability to create or use in-house tests. On April 29, 2024, the FDA announced a final rule establishing its jurisdiction over LDTs—but what led up to this rule . . . and what will happen next?

THE HISTORY OF LDT REGULATIONS IN THE US
1938The Federal Food, Drug, and Cosmetic Act (FFDCA) passes, giving the FDA authority to regulate the quality, safety, and efficacy, and label accuracy of drugs and other products.4 In its original form, the Act does not mention medical devices.
1944With the passage of the Public Health Service Act, the federal government acquires new responsibilities, which include certifying medical laboratories.
1967The Clinical Laboratories Improvement Act of 1967 introduces licensing, regulation, and quality requirements for clinical laboratories—but only those operating across state or country lines.
1969A court case, United States v. Bacto-Unidisk, debates whether an antibiotic sensitivity disc designed for drug selection constitutes a “drug” or merely a “device” to determine whether such devices must be cleared by the FDA. The U.S. Supreme Court ultimately rules that, because the device contains a drug, premarket clearance is required.
1972The FDA proposes to regulate in vitro diagnostics, a rapidly growing field, on the basis that—as medical devices—they fall under the FFDCA. The proposed rule covers labeling, performance, and reliability standards.
1976The Medical Device Amendments of 1976 (MDA) explicitly places all medical devices under the FDA’s jurisdiction. The amendments create three risk-based device classes, establish regulatory pathways, and allow the FDA to ban unsafe devices.
1977The FDA publishes a final rule on medical devices, which exempts clinical laboratories from the MDA and also exempts devices “intended solely for use by a physician . . . not generally available to, or generally used by, other physicians”—including LDTs.
1988The Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88) defines regulatory requirements for all clinical laboratories. These include certification, accreditation, inspection, and standards for quality and proficiency.
1992In a draft compliance policy guide on tests labeled for research use only, the FDA notes that some such tests are being used or commercialized for diagnostic purposes. Asserting that such devices are “subject to the same regulatory requirements as any unapproved medical device,” the draft proposes a certification program, but exempts tests “essential to public health.”
1997The FDA publishes a final rule on analyte-specific reagents, which states that labs using LDTs are “acting as manufacturers of medical devices and are subject to FDA jurisdiction,” but declines a suggestion to classify all LDTs as class II or III medical devices.
2003Amendments to CLIA ’88 introduce additional requirements for LDT performance verification, but place LDTs outside the FDA’s purview by referring to “methods developed in-house” as “test system[s] not subject to FDA clearance or approval.”
2014Draft guidance from the FDA focuses specifically on LDTs, declaring that the agency no longer considers its historical enforcement discretion appropriate and proposing that labs who develop LDTs should be held to the same standards as commercial manufacturers of in vitro diagnostic devices.
2016The House Committee on Appropriations directs the FDA to suspend its efforts to regulate LDTs,1 resulting in the agency’s withdrawing its draft guidance document and continuing the conversation with a discussion paper on LDT oversight.
2020The Verifying Accurate Leading-edge IVCT Development Act is firstintroduced in Congress; although never passed, it outlines the FDA’s intent to regulate all in vitro clinical tests, including LDTs.
2023The FDA announces a proposed rule to make it explicit that the agency has jurisdiction over all in vitro diagnostics, “including when the manufacturer . . . is a laboratory” and to phase out its discretionary approach to enforcement with respect to LDTs.
2024The FDA publishes its final rule on LDTs, as well as two related draft guidance documents: one on enforcement discretion in declared emergency situations and one on discretion in the absence of a declared emergency.
FDA LAB-DEVELOPED TEST PHASEOUT DEADLINES
2025Stage 1 of the FDA’s enforcement discretion phaseout process requires compliance with medical device reporting requirements, correction and removal reporting requirements, and quality system requirements regarding complaint files.
2026Stage 2 requires compliance with any requirement not covered in other phases.
2027Stage 3, which begins in May, requires compliance with quality system requirements other than for complaints.
Stage 4, which begins in November, requires high-risk LDTs to comply with premarket review requirements unless a premarket submission has been received.
2028Stage 5, the final stage of the phaseout process, expands premarket review requirement compliance to low- and moderate-risk LDTs for which a premarket submission has not been received.

Still have questions about LDT regulation? Join Today's Clinical Lab and G2 Intelligence for a free webinar to discuss what steps clinical lab leaders will need to take to ensure they are prepared for the FDA's new LDTs rule.

Reference:

  1. U.S. Congress House Committee on Appropriations. “29. Laboratory Developed Tests.” In Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations for 2018: USDA Office of the Inspector General, 257–258. Washington, D.C.: U.S Government Publishing Office, 2017.

Michael Schubert, PhD

Michael Schubert, PhD, is a veteran science and medicine communicator. He holds graduate degrees in biochemistry and molecular biology with a research focus on chromatin structure and function and has written on subjects from subspeciality pathology to fictional science. In addition to writing and editing, he is co-director of the Digital Communications Fellowship in Pathology and professor of professional practice in academic writing at ThinkSpace Education, the University of Chichester.


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With LDTs being regulated in the same way as commercially manufactured and marketed diagnostics, many labs lack the resources to comply, limiting their ability to create or use in-house tests.
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