The U.S. Food and Drug Administration (FDA or the Agency) recently proposed a new rule that has sparked controversy. The regulatory landscape for laboratory developed tests (LDTs) would completely shift under the proposed rule.  FDA has long considered LDTs to be medical devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act). But, for nearly 50 years, the Agency has exercised “enforcement discretion” and not actively regulated most LDTs under FDA’s pre- and post-market medical device regulatory authorities. Instead, developers of LDTs have largely been subject to clinical laboratory regulatory requirements administered by the Centers for Medicare & Medicaid Services (CMS). Citing public health concerns and Congressional inaction in implementing diagnostics regulatory reform, FDA announced in its proposed rule that it intends to phaseout the historical enforcement discretion policy for LDTs.

FDA defines an LDT as an in vitro diagnostic (IVD) that is intended for clinical use and that is designed, manufactured, and used within a single certified laboratory that meets the regulatory requirements under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high complexity testing. The proposed rule adds a single sentence to the IVD product regulations at 21 CFR Part 809 clarifying that IVDs are considered medical devices even when the manufacturer of the product is a laboratory. If finalized, the rule would implement a four-year plan to subject LDTs to FDA’s pre- and post-market medical device regulatory requirements. In the preamble to the proposed rule, FDA estimates that approximately 50% of LDTs would require Agency premarket review under the new policy.

Certain clinical laboratory stakeholders – like the American Clinical Laboratory Association – have long questioned FDA’s statutory authority to regulate LDTs as medical devices and have already called upon the Agency to withdraw the proposed rule. Some in the clinical laboratory community continue to advocate for diagnostics regulatory reform through a federal legislative solution, such as the Verifying Accurate, Leading-edge IVCT Development (VALID) Act. Other organizations claim that FDA should have no regulatory authority over LDTs, and that developers of such tests should only be subject to CMS jurisdiction and efforts to modernize the CLIA regulatory framework.

On the same day FDA released the proposed rule, U.S. Senator Bill Cassidy, M.D. (R-LA), ranking member of the Senate Health, Education, Labor, and Pensions (HELP) Committee stated: “The FDA does not have the authority to unilaterally expand its regulatory jurisdiction . . . While past legislative efforts may have missed the mark, it is time for Congress to assert itself and clarify FDA’s authority in the regulation of diagnostic tests.” Absent Congressional action in the interim, there will likely be legal challenges if FDA ultimately finalizes the LDT rule.

Key aspects of the proposed rule are outlined below.

FDA’s enforcement discretion phaseout policy contains five stages over a four-year period after the finalization of the rule:

FDA is proposing to exercise enforcement discretion indefinitely for certain categories of LDTs:

• Tests intended solely for forensic (law enforcement) purposes.
• Tests exclusively used for public health surveillance.
• Certain Human Leukocyte Antigen (HLA) tests.
• “1976-Type LDTs” that have the following common characteristics: use of manual techniques (without automation) performed by laboratory personnel with specialized expertise; use of components legally marketed for clinical use; and designed, manufactured, and used within a single certified laboratory that meets the requirements under CLIA for high complexity testing.

FDA reiterates that the following categories of tests have historically not been considered subject to the Agency’s LDT enforcement discretion and, as a result, are not subject to the proposed phaseout policy described in the proposed rule:

• Direct-to-consumer tests that lack meaningful involvement by a licensed healthcare professional.
• Tests intended for emergencies, potential emergencies, or material threats declared under FD&C Act § 564.
• Tests that are intended as blood donor screening or human cells, tissues, and cellular and tissue-based products (HCT/Ps) donor screening tests required for infectious disease testing or for the determination of blood group and Rh factors.

FDA has asked stakeholders to provide specific feedback on the following topics, among others:

• Whether the Agency should maintain its current enforcement discretion approach with respect to premarket review and some or all QS requirements for currently marketed LDTs (i.e., “grandfathering”).
• How the proposed phaseout policy may have unintended consequences for certain patient populations (e.g., Medicare beneficiaries, rural populations) and what steps could be taken to alleviate those consequences.
• Public health rationales for having a longer phaseout period for LDTs offered by laboratories with annual receipts below a certain threshold (e.g., $150,000).
• The definition of “academic medical center” (AMC) and whether FDA should implement a different phaseout approach for AMC laboratories.
• How FDA might leverage programs such as the New York State Department of Health Clinical Laboratory Evaluation Program (NYSDOH CLEP) or those within the Veterans Health Administration (VHA) as part of the phaseout approach.
• Any implications of continued enforcement discretion for LDTs used for law enforcement purposes and any factors that FDA should consider – particularly as it relates to civil rights and equity – regarding the scientific validity and accuracy of such tests.

Interested parties have 60 days to submit public comments to FDA concerning the proposed rulemaking under docket number FDA-2023-N-2177 at www.regulations.gov.