Department of Health & Human Services (HHS) / Food & Drug Administration (FDA) Centers for Medicare & Medicaid Services (CMS)

• 21 C.F.R. § 809.10 — “Labeling for Laboratory Use” exemption for RUO/LDTs. • 21 C.F.R. § 820.30(i) — “Custom Device” carve-out under the Quality System Regulation. • FDA Enforcement Policy for Laboratory-Developed Tests (e.g. the 2014 draft guidance) — rescind FDA’s guidance that declares enforcement discretion for LDTs. • 42 C.F.R. § 493.3 — amend or repeal the definitions of “waived test” and “provider-performed microscopy” that underpin CMS’s CLIA-only oversight of LDTs.

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Notice of Proposed Rulemaking

Safe-Harbor Exemptions for Laboratory-Developed Tests (“LDT Oversight Exemptions”)

FDA has long allowed high-risk LDTs to enter clinical use without premarket review, quality-system controls, or post-market surveillance by: • Exempting RUO/LDTs from registration and clearance (21 C.F.R. § 809.10) • Treating them as “custom devices” outside QSR requirements (21 C.F.R. § 820.30(i)) • Declaring formal enforcement discretion via agency guidance • Relying solely on CLIA definitions that bar FDA inspection of LDT analytic performance (42 C.F.R. § 493.3) Removing these carve-outs will require all laboratory tests used for patient care to undergo the same FDA premarket authorization, QSR, and post-market monitoring as other in vitro diagnostics—closing safety and quality gaps that have led to diagnostic errors and patient harm.

Department of Health & Human Services Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

(301) 492-4305 (410) 786-1524 (410) 786-8437

Beginning in the 1990s, FDA’s IVD regulations (21 C.F.R. Part 809 and Part 820) included carve-outs for “for laboratory use only” products and “custom devices,” which laboratories leveraged to deploy LDTs without FDA clearance. In parallel, CMS’s CLIA rules (42 C.F.R. Part 493) and CMS’s interpretation of “waived tests” and “provider-performed microscopy” insulated LDT analytic performance from FDA oversight. In 2014, FDA codified its de facto hands-off approach by issuing draft guidance that claimed enforcement discretion for LDTs. High-profile failures—such as mis-validated COVID-19 LDTs—have demonstrated the risks of leaving these tests unregulated.

• 21 C.F.R. § 809.10: Eliminating the RUO/LDT exemption forces clinical labs to register, list, and seek FDA clearance or approval for in vitro diagnostics used in patient care. • 21 C.F.R. § 820.30(i): Removing the custom-device carve-out brings LDT manufacturing and design under full QSR (design control, process validation, CAPA). • FDA LDT Enforcement Guidance: Rescinding the guidance removes any agency-declared safe harbor, making each LDT subject to statutory FDA enforcement under the FD&C Act. • 42 C.F.R. § 493.3: Amending the “waived test” and “provider-performed microscopy” definitions ensures CLIA cannot preempt FDA’s authority to inspect analytic performance.

— 21 C.F.R. § 809.10 deleted; no “for laboratory use only” class—every laboratory assay for patient diagnosis must comply with IVD registration, listing, and authorization. — 21 C.F.R. § 820.30(i) removed; “custom devices” are no longer exempt—LDTs must meet all QSR requirements in 21 C.F.R. Part 820. — FDA LDT Enforcement Guidance rescinded; no policy statement granting enforcement discretion—all LDTs are subject to the same statutory premarket and inspection standards under the FD&C Act. — 42 C.F.R. § 493.3 amended to remove CLIA definitions that limit CMS oversight—in vitro diagnostic performance is subject to concurrent FDA and CMS inspection and enforcement.

Robert F. Kennedy Jr.

Secretary of Health and Human Services