Diagnostic Tests are Generally Regulated as Devices

The Federal Food, Drug, and Cosmetic Act’s (FDCA’s) definition of “device” include “in vitro reagent” that “is intended for use in the diagnosis of a disease or other conditions . . . .” Thus, in vitro diagnostic products (IVDs) are considered devices under the FDCA, and are generally subject to FDA’s premarket and postmarket requirements, including clearance or approval, quality controls for manufacturing and distribution, and specific labeling requirements. Many genetic tests are IVDs, as are tests used in genomics, personalized medicine, and with digital health technologies to identify whether a patient is likely to benefit from a particular treatment.

FDA generally regulates IVDs according to the agency’s device risk classification system: ranging from Class I to Class III, the higher the device classification, the more FDA regulations the developer/manufacturer must follow, and the longer the statutory timeline for the device to be legally marketed. IVDs are also subject to requirements and categorization under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).

FDA’s Proposed Rule Would Regulate all LDTs as IVDs

Laboratory developed tests (LDTs) have long been distinguished from IVDs because of differences in development, implementation, and use. IVDs are diagnostic tests that manufacturers sell to laboratories as complete “kits,” and come with all components – reagents, controls, and procedures – that a laboratory needs to perform the test. LDTs are designed, manufactured, and performed entirely within a single laboratory. This distinction presents an important legal and jurisdictional issue.

FDA first asserted its authority over LDTs in 1992, but this authority has long been challenged. The agency issued Draft Guidance documents in 2006, 2007, and 2014. In 2017, instead of issuing Final Guidance, FDA released a “Discussion Paper” that synthesized feedback from the 2014 Draft Guidance and follow-up meetings with stakeholders. The Discussion Paper specifically disclaimed representing any agency position. Meanwhile, FDA largely exercised “enforcement discretion” over LDTs. This created years of confusion and uncertainty for the laboratory industry. (For Penn Avenue Law & Policy’s detailed analysis of the history of FDA’s attempt to regulate LDTs, see here and here).

On October 3, 2023, FDA published in the Federal Register a proposed rule that seeks to amend the definition of IVDs to explicitly include tests “manufactured” in a laboratory, thus subjecting LDTs to FDA regulation as medical devices. Specifically, FDA’s proposed rule seeks to amend the definition of IVDs under 21 C.F.R. sec. 809.3(a) to make explicit that LDTs are IVDs under the FDCA. If the rule is finalized, IVDs would be defined as:

“[t]hose 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 … including when the manufacturer of those products is a laboratory.

FDA’s proposed rule adds the final clause, indicated here in bold, italicized text. If laboratories are explicitly included in the IVD definition as manufacturers, LDTs will be subject to premarket submission requirements. Laboratories will generally have to submit a 510(k), De Novo, or PMA application before tests can be offered for use, and will have to comply with FDA requirements governing registration and listing, quality systems, labeling, medical device reporting, corrections and removals, and clinical trials. These requirements differ from, and in some ways conflict with, CLIA.

FDA’s proposed rule also includes a proposed five-stage “phaseout policy,” under which the agency would phaseout its exercise of enforcement discretion for LDTs. For further details about the proposed phaseout policy, see Penn Avenue Law & Policy’s analysis here.

Comments to FDA’s proposed rule were due on December 4, 2023. Stakeholders submitted thousands of comments before that deadline, which demonstrates the long-standing disagreement regarding FDA’s jurisdiction over LDTs and concerns about how FDA’s regulation of LDTs as medical devices will impact laboratory performance, access to tests, and public health. The laboratory industry must wait and see whether FDA will proceed with a final rule to regulate LDTs.

All Laboratories Must Comply with CLIA Requirement

Through CLIA, the Center for Medicare & Medicaid Services (CMS) regulates all non-research laboratory tests performed on humans in the United States. Before a laboratory can accept human specimens for testing, it must have CLIA certification. CLIA certificates vary based on the types and complexities of tests performed by the laboratory.

CMS’ objective under CLIA is to ensure that laboratories performing tests on human specimens produce accurate and reliable test results. Under the FDCA, FDA regulates devices, including IVDs, to ensure that they are reasonably safe and effective. Laboratories manufacturing or developing IVDs, must be aware of and comply with FDA and CLIA requirements. It is important to note that some requirements under these systems that are not consistent. 

Christine P. Bump has Extensive Experience Regarding the Regulation of Diagnostic Tests

There remains a lot of uncertainty regarding the regulation of diagnostic tests, and how laboratories consistently comply with both FDA requirements and CLIA. Whether your test is an IVD device, an LDT, or being combined with a personalized medicine/digital health technology, you need legal counsel who is experienced at navigating these pathways. Christine P. Bump has extensive experience advising clients on the regulations, guidance, and policies applicable to laboratories and tests, and developing regulatory strategies for diagnostic tests, even when pathways are not clearly defined.

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