LDT vs IVD: What Changed for Oncology Biomarker Tests

LDT vs IVD: What Changed for Oncology Biomarker Tests

Between May 2024 and September 2025, the US rules for laboratory developed tests (LDTs) changed twice. The FDA published a final rule that would have phased out its long-standing enforcement discretion and brought most LDTs under device regulation. A federal court vacated that rule in March 2025, and in September 2025 the FDA formally removed it from the Code of Federal Regulations.

For oncology biomarker teams, the headline is simple: the FDA LDT rule is gone, and LDTs are back where they were before 2024, overseen by CMS under CLIA, with the FDA exercising enforcement discretion. The detail matters more. None of this changed what a drug sponsor needs for a companion diagnostic (CDx) claim, and the debate has moved to Congress and to CMS, which reopened the CLIA regulations for comment in July 2026.

This article sets out the FDA’s current position as of 13 October 2026, explains the LDT vs IVD distinction for NGS panels, IHC and MRD assays, and covers what pharma and diagnostics partners should do now.

Key takeaways

• The FDA’s May 2024 LDT final rule was vacated on 31 March 2025 by the US District Court for the Eastern District of Texas in American Clinical Laboratory Association v. FDA, consolidated with Association for Molecular Pathology v. FDA. The FDA did not appeal.
• On 19 September 2025, the FDA published a final rule restoring the pre-2024 definition of in vitro diagnostic products in 21 CFR 809.3. Every phase-out deadline in the 2024 rule is void.
• LDTs remain regulated by CMS under CLIA. In July 2026, CMS and CDC published a request for information on updating the CLIA regulations, including validation of tests that are not FDA cleared or approved.
• The Enhancing CLIA Act of 2026 (H.R. 8890), introduced in May 2026, would declare LDTs not to be devices and expand CLIA oversight. It is a bill in committee, not law.
• A CDx claim in a drug label still requires FDA authorisation of the test, usually through PMA, plus investigational device requirements during the trial. The LDT ruling did not change that.

The FDA LDT rule: what happened, in order

The court ruling

Judge Sean D. Jordan held that an LDT is a professional service rather than a manufactured device, and that Congress gave oversight of laboratory testing to CMS through CLIA rather than to the FDA through the Food, Drug, and Cosmetic Act. The opinion relied on the Supreme Court’s 2024 decision in Loper Bright Enterprises v. Raimondo, which ended judicial deference to agency readings of ambiguous statutes. The first stage of the phase-out, covering adverse event reporting and complaint files, had been due to start on 6 May 2025. It never took effect.

The rescission

The FDA’s LDT page (content current as of 19 September 2025) states that the agency issued a final rule reverting the regulation to its text before the 2024 rule. In practice, the FDA is back to the enforcement discretion policy it has applied to most LDTs for decades. That discretion is a policy choice rather than an exemption, and the FDA still regards test kits, components and software distributed to other laboratories as devices.

Congress and CMS

The VALID Act, which would have created a new FDA category of “in vitro clinical tests” with risk-based premarket review, was considered in several Congresses, left out of the 2022 user fee legislation and never enacted. The bill now in play is the Enhancing Clinical Laboratory Innovation and Access Act of 2026, which goes the other way: it would confirm that LDTs are not devices and would direct CMS to strengthen CLIA, including a public database of LDT performance and validation information and centralised error reporting. ACLA has backed it. As of October 2026, it sits with the House Energy and Commerce and Ways and Means committees.

Separately, the CMS and CDC request for information, published on 16 July 2026, is the first broad review of the CLIA regulations at 42 CFR part 493 since they took effect in 1992. It asks, among other things, how laboratories should establish performance specifications for tests that are not FDA cleared or approved. An RFI creates no new requirements, but it is the most likely route to tighter LDT validation rules in the near term.

LDT vs IVD vs CDx: the definitions that matter

An LDT is a test designed, validated and performed within a single CLIA-certified laboratory. CLIA certifies the laboratory and checks analytical validity, quality systems and proficiency testing. It does not review clinical validity or the claims a laboratory makes about a test.

An IVD is a test kit or system made by a manufacturer and distributed to laboratories. It needs FDA clearance or approval: 510(k) for most moderate-risk tests with a predicate, De Novo for novel low to moderate-risk tests, and premarket approval (PMA) for class III tests.

A companion diagnostic is an IVD that provides information essential for the safe and effective use of a corresponding drug, as defined in the FDA’s 2014 guidance on in vitro companion diagnostic devices. Most oncology CDx are class III and are approved through PMA, ideally at the same time as the drug. Our step-by-step guide to the FDA companion diagnostic approval process covers the pathway in detail, and our piece on companion vs complementary diagnostics explains when a test is essential rather than informative.

How LDTs are used in oncology

LDTs carry a large share of US oncology biomarker testing.

• NGS panels. Many reference laboratories and academic centres run comprehensive genomic profiling panels as LDTs, often alongside FDA-approved panels. The LDT versions tend to cover more genes, update faster and serve indications where no CDx exists.
• IHC. Pathology laboratories often use laboratory-validated IHC protocols, or modify approved kits by changing the antibody, platform or scoring, which turns the test into an LDT.
• MRD and ctDNA. Most tumour-informed and tumour-naive ctDNA MRD assays used in clinical practice and in trials are LDTs. Our article on ctDNA and MRD in immunotherapy trials covers how they are used as trial endpoints and enrichment tools.
• Clinical trial assays. Before a CDx exists, patients are often enrolled with a central laboratory LDT, which later has to be bridged to the commercial test.

The 2025 ruling preserved this ecosystem. Laboratories will not need to file the PMAs and 510(k)s the 2024 rule would have required from November 2027 and May 2028.

What pharma needs for a CDx claim, whatever happens to LDTs

The vacatur covers laboratory tests offered as a service. It did not touch the drug side of the equation. If a drug’s safe and effective use depends on a biomarker result, the FDA expects an approved or cleared CDx, and the drug label will refer to “an FDA-approved test”. An LDT, however good, cannot carry that claim.

During the trial

An investigational test used to select or assign patients is subject to the investigational device exemption (IDE) rules in 21 CFR part 812. Depending on risk, the study may need an IDE, may be non-significant risk or may be exempt. For oncology programmes, the FDA’s 2019 guidance on a streamlined submission process for study risk determination lets sponsors include test information in the IND so that CDER consults CDRH, instead of filing a separate Q-submission.

Bridging

If patients were enrolled with a clinical trial assay (often an LDT) that differs from the final CDx, the sponsor needs a bridging study, usually re-testing banked trial samples with the final test and showing concordance and preserved clinical effect. Missing samples and analytical drift between the two assays are the usual problems, so lock down sample banking and consent early.

Approval

Most oncology CDx go through PMA, coordinated with the drug NDA or BLA. FDA’s 2020 guidance on labelling CDx for a specific group of oncology therapeutic products allows a test to claim a class of drugs where the evidence supports it, which helps NGS panels. On co-development structure, see our guide to structuring pharma–diagnostics CDx partnerships.

New York CLEP and payer coverage

New York. Any laboratory testing specimens from New York, wherever it is located, needs a New York State clinical laboratory permit, and the Wadsworth Center’s Clinical Laboratory Evaluation Program (CLEP) reviews LDTs before they can be used on New York patients, using a tiered, risk-based approach. With no federal premarket review, CLEP approval is the closest thing to an independent check on clinical validity that many national laboratories have, and pharma partners often ask for it.

Medicare. Coverage creates its own evidence bar. Under National Coverage Determination 90.2 (current version effective 27 January 2020), NGS for patients with advanced cancer is nationally covered when the test is FDA approved or cleared as a companion in vitro diagnostic and the patient’s cancer is within its indication. Other NGS tests, including LDTs, can be covered at the discretion of the Medicare Administrative Contractors. In many states, that decision runs through Palmetto GBA’s MolDX programme, which requires test registration and a technical assessment of analytical and clinical validity and clinical utility. FDA authorisation is therefore a payer advantage as well as a labelling one.

How the EU compares

The EU went the opposite way. Under the In Vitro Diagnostic Regulation (IVDR), tests made and used within a health institution can rely on the Article 5(5) in-house exemption only if conditions are met: an appropriate quality management system, EN ISO 15189 compliance (or national equivalent), no transfer to another legal entity, and public declarations. From 26 May 2028, point (d) also requires the institution to justify why an equivalent CE-marked device cannot meet the target patient group’s needs. Commercial reference laboratories cannot use the exemption at all, and an EU CDx needs notified body certification with consultation of the EMA or a national medicines authority. Our IVDR companion diagnostics guide covers the EU pathway and timelines.

For a global programme, that means a US strategy built on LDTs does not transfer to Europe, where the default expectation is a CE-marked CDx.

What to do now: a checklist for oncology biomarker teams

• Retire any 2024 rule compliance plans (MDR reporting, QMS upgrades, premarket submissions for LDTs) that were justified only by the phase-out timetable, but keep any that add quality value.
• Do not let the ruling change CDx planning. If the biomarker selects patients, budget for an IDE assessment, a final assay locked before the pivotal trial and a PMA.
• If you enrol with an LDT clinical trial assay, plan the bridging study from day one: sample banking, consent for re-testing and a concordance plan.
• When choosing a laboratory partner, ask for CLIA certification, CAP accreditation, NY CLEP approval status and MolDX technical assessment history.
• Track H.R. 8890 and any Senate companion, and watch for a CLIA proposed rule following the July 2026 RFI.
• For EU trials and launches, assume IVDR applies: confirm whether a CE-marked CDx exists, and if your partners rely on Article 5(5), check that they can document point (d) before May 2028.
• Keep an eye on FDA statements about LDTs used with drugs; the agency still claims authority over kits and distributed components.

Discuss CDx regulation at ImmunoMark San Diego

US CDx strategy is a core theme of the Biomarkers, Companion Diagnostics & Precision Medicine stream at the immuno-oncology and companion diagnostics conference in San Diego on 10–11 February 2027. Day 2 includes “Global Regulatory Strategies for Companion Diagnostics and Precision Medicine” and “Market Access and Reimbursement Strategies for Companion Diagnostics in Precision Oncology” runs on Day 1, alongside pre-arranged 1:1 meetings and a Day 1 drinks reception. The launch edition expects 300+ senior attendees from pharma, biotech and diagnostics.

For the EU and UK view, the London edition on 3–4 March 2027 includes “Panel: Global CDx Approval Pathways – EMA, FDA & MHRA Perspectives”.

Register for ImmunoMark San Diego 2027

If your company wants to meet this audience directly, whether you run a CLIA laboratory, develop CDx or support regulatory strategy, see the San Diego 2027 sponsorship packages or our overview of sponsoring a companion diagnostics conference in San Diego.

FAQs

Is the FDA LDT rule still in effect?

No. The US District Court for the Eastern District of Texas vacated the May 2024 rule on 31 March 2025 in American Clinical Laboratory Association v. FDA, the FDA did not appeal, and on 19 September 2025 the FDA published a final rule restoring the pre-2024 text of 21 CFR 809.3. LDTs are again overseen by CMS under CLIA, with the FDA exercising enforcement discretion.

What is the difference between an LDT and an IVD?

An LDT is designed, validated and performed within a single CLIA-certified laboratory and is not reviewed by the FDA. An IVD is a test kit or system distributed to laboratories and needs FDA clearance or approval through 510(k), De Novo or PMA. A companion diagnostic is an IVD essential for the safe and effective use of a specific drug.

Can an LDT be used as a companion diagnostic?

An LDT can be used to enrol patients in a trial, subject to investigational device rules, and laboratories can offer LDTs for approved biomarkers. But a CDx claim in a drug label requires an FDA-authorised test, usually through PMA. If the trial used an LDT, the sponsor needs a bridging study to the final CDx.

Is there new LDT legislation in 2026?

The Enhancing Clinical Laboratory Innovation and Access Act of 2026 (H.R. 8890) was introduced on 19 May 2026. It would confirm that LDTs are not medical devices and strengthen CMS oversight under CLIA. As of October 2026 it is in committee. CMS and CDC also published a request for information on updating the CLIA regulations in July 2026.

How does the EU regulate in-house tests compared with US LDTs?

Under IVDR Article 5(5), health institutions can make and use in-house tests without a notified body only if they meet conditions including a quality management system, EN ISO 15189 compliance and no transfer to another legal entity, and from 26 May 2028 a justification that no equivalent CE-marked device meets patient needs. Commercial laboratories cannot use the exemption.