The Complex World of Diagnostics Regulation: FDA & LDTs

In-vitro diagnostic products (IVDs) are the backbone of modern medicine, providing the crucial data used to diagnose, monitor, and prevent diseases. Given their profound impact on patient health, IVDs—which include reagents, instruments, or other systems—are regulated as medical devices in the United States. Understanding the multilayered regulatory structure overseen by the Food and Drug Administration (FDA) is essential for any company operating in this space.

This article provides an in-depth look at the regulatory landscape, focusing on the classification system, premarket pathways, postmarket requirements, and the recent, highly contentious debate surrounding Laboratory Developed Tests (LDTs).

The Foundational Framework: IVDs Under the FDCA

The regulatory authority for IVDs stems primarily from the Federal Food, Drug, and Cosmetic Act (FDCA). The FDA’s Center for Devices and Radiological Health (CDRH) is the main body responsible for overseeing IVD safety and effectiveness, although some products, like blood screening tests, fall under the Center for Biologics Evaluation and Research (CBER).

Risk-Based Classification System

The FDA classifies all medical devices, including IVDs, into three classes based on the risk they pose to the patient and the level of regulatory control needed to ensure safety and effectiveness.

Premarket Review Pathways

• Premarket Notification (510(k)): Required for most Class II devices, this process requires demonstrating that the new device is “substantially equivalent” (SE) to a legally marketed predicate device.
• Premarket Approval (PMA): This is the most stringent review, typically for Class III devices. It requires comprehensive scientific evidence to prove the safety and effectiveness of the device.
• De Novo Classification: This pathway is for novel, low-to-moderate risk devices (new types of Class I or Class II) for which there is no legally marketed predicate. It allows the FDA to classify the device and establish special controls for future similar devices.

The LDT Conundrum: A Shifting Regulatory Landscape

A Laboratory Developed Test (LDT) is an IVD that is designed, manufactured, and used within a single laboratory. For decades, while the FDA maintained that LDTs met the statutory definition of a medical device, the agency exercised “enforcement discretion,” meaning it chose not to enforce premarket review and most other regulatory requirements for these tests. This traditional policy stemmed from a time when LDTs were simpler and used on a limited, on-site basis.

The FDA’s Attempted Policy Shift

Due to the increasing complexity, volume, and public health significance of LDTs (e.g., genomic testing, sophisticated infectious disease diagnostics), the FDA has repeatedly signaled its intent to phase out enforcement discretion.

A notable recent action was the FDA’s Final Rule, published in May 2024, which explicitly amended the regulations to clarify that IVDs are devices even when the manufacturer is a laboratory. This rule outlined a multi-year, phased approach to begin applying standard medical device requirements (such as adverse event reporting, quality systems, and eventually premarket review) to LDTs.

Essential Postmarket & Concurrent Compliance

Quality System Regulation (QSR) / QMSR

All device manufacturers must comply with the Quality System Regulation (QSR), which covers the methods and controls used for designing, manufacturing, packaging, labeling, and servicing medical devices (21 CFR Part 820). In 2024, the FDA issued the Quality Management System Regulation (QMSR) Final Rule, which aims to harmonize U.S. requirements by largely incorporating the international standard ISO 13485. While manufacturers must comply with the QSR until the QMSR rule becomes fully effective (in early 2026), the shift is a major compliance consideration.

Medical Device Reporting (MDR)

Manufacturers are required to report certain adverse events and product malfunctions to the FDA under the Medical Device Reporting (MDR) program (21 CFR Part 803). This is a critical postmarket surveillance tool used to identify and monitor significant problems with devices.

The Role of CLIA ’88

The Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88) represent a separate, parallel regulatory framework for diagnostic testing. CLIA establishes quality standards for laboratory testing based on test complexity (waived, moderate, or high complexity), governing personnel, quality control, and proficiency testing. It is essential to understand that compliance with CLIA does not exempt a test from FDA device regulations.

Summary: Navigating the Regulatory Currents

The regulation of diagnostic tests is a complex, continuously evolving area that demands proactive compliance and close monitoring of administrative and judicial developments. Success in the IVD market hinges on a deep understanding of the risk-based framework and the current regulatory status of your product.

1. The FDA regulates all IVDs as medical devices under the FDCA, classifying them into Class I, II, or III based on risk, which dictates the required premarket pathway (exemption, 510(k), De Novo, or PMA).
2. The regulatory environment for Laboratory Developed Tests (LDTs) is highly volatile, with the FDA asserting authority but facing legal challenges to its efforts to phase out decades of enforcement discretion.
3. All IVD manufacturers must adhere to rigorous postmarket controls, including the Quality System Regulation (QSR) (soon to be QMSR) for manufacturing quality, and the Medical Device Reporting (MDR) system for tracking adverse events.
4. In addition to FDA device regulation, clinical laboratories must also comply with the separate, quality-focused standards established by the Clinical Laboratory Improvement Amendments (CLIA ’88).
5. Companies must ensure stringent compliance with labeling and usability requirements, especially for Over-the-Counter (OTC) or Direct-to-Consumer diagnostic products.

Frequently Asked Questions (FAQ)

What is the main difference between FDA and CLIA regulation for diagnostics?

The FDA regulates IVDs as medical devices, focusing on the safety and effectiveness of the product itself for commercial distribution. CLIA (CMS) regulates the quality of the laboratory performing the test, ensuring accuracy and reliability of the testing process, regardless of whether the test is an FDA-approved device or an LDT.

If an LDT is grandfathered, does it still have to comply with any FDA rules?

Yes. Even under enforcement discretion policies, the FDA generally retains the ability to take enforcement action against any “violative” LDT at any time. Furthermore, even the vacated Final Rule acknowledged limited enforcement discretion for certain LDT categories, but still required compliance with core requirements like Medical Device Reporting (MDR) and complaint files.

What is a “predicate device” in the context of 510(k)?

A predicate device is a legally marketed device to which a new device is compared to establish “substantial equivalence” for a 510(k) submission. If the new device is found to be substantially equivalent to the predicate (and the predicate is not a Class III device requiring PMA), it is cleared for market.

What happens if a diagnostic device is found to be “adulterated” or “misbranded”?

Devices found to be adulterated (e.g., failing to meet QSR standards) or misbranded (e.g., false or misleading labeling) are subject to a range of administrative and judicial sanctions by the FDA, including warning letters, restrictions on manufacturing, civil penalties, or product recalls.

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FDA, In Vitro Diagnostics (IVD), Laboratory Developed Tests (LDTs), Medical Devices, FDCA, Premarket Approval (PMA), 510(k), Quality System Regulation (QSR), CLIA ’88, Enforcement Discretion, Companion Diagnostics, CDRH, Diagnostic Testing, Regulatory Compliance