FDA summarizes LDT rule requirements in new compliance guide

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FDA summarizes LDT rule requirements in new compliance guide

27 June 2024

The U.S. Food and Drug Administration (FDA) announced yesterday a “Small Entity Compliance Guide” (SECG) for Laboratory Developed Tests (LDTs), aiming to assist small entities in complying with FDA’s LDT final rule, which would regulate in vitro diagnostic (IVD) products and LDTs as “devices” under the Federal Food, Drug, and Cosmetic Act (FDCA), should the final rule take effect on July 5. We have summarized the SECG below, including FDA’s enforcement timeline for the LDT final rule.

FDA’s LDT final rule published in May 2024 amends FDA’s regulations to make explicit that IVDs will be regulated as “devices” under the Federal Food, Drug, and Cosmetic Act (FDCA), including when the manufacturer of the IVD is a laboratory, as we recently analyzed online here. Now, FDA has published a corresponding LDT small entity compliance guide (SECG), aiming to help small entities comply with medical device regulations that are consistent with the LDT final rule, including the phasing out of FDA’s general enforcement discretion approach for LDTs.

Table 2 of the SECG resembles the infographic below depicting the FDA’s enforcement expectations (some information redacted for ease of reading):

Category of IVD	Stage 1: Medical Device Reporting Reporting of Corrections and Removals Complaint Files	Stage 2: Requirements Not Covered In Other Stages, Including: Establishment Registration & Device Listing Labeling Investigational Use Requirements	Stage 3: Quality System Requirements other than Complaint Files	Stages 4 & 5: Premarket Review
Donor screening tests for infectious diseases and certain blood typing tests	compliance currently expected	compliance currently expected	compliance currently expected	compliance currently expected
Direct-to-Consumer (DTC) tests	compliance currently expected	compliance currently expected	compliance currently expected	compliance currently expected
Public Health Surveillance tests	compliance generally not expected	compliance generally not expected	compliance generally not expected	compliance generally not expected
1976 type LDTs	compliance generally not expected	compliance generally not expected	compliance generally not expected	compliance generally not expected
HLA tests for transplantation	compliance generally not expected	compliance generally not expected	compliance generally not expected	compliance generally not expected
Forensic tests	compliance generally not expected	compliance generally not expected	compliance generally not expected	compliance generally not expected
LDTs manufactured and performed within DoD and VHA	compliance generally not expected	compliance generally not expected	compliance generally not expected	compliance generally not expected
LDTs for unmet needs manufactured and performed by labs integrated in the healthcare system treating the patient	compliance generally expected beginning May 6, 2025	compliance generally expected beginning May 6, 2026	compliance with 21 CFR 820.180-820.186 generally expected beginning May 6, 2027; compliance generally not expected with other QS requirements (except for complaint files)	compliance generally not expected
Currently marketed IVDs offered as LDTs first marketed prior to rule publication date and not modified beyond scope described in preamble	compliance generally expected beginning May 6, 2025	compliance generally expected beginning May 6, 2026	compliance with 21 CFR 820.180-820.186 generally expected beginning May 6, 2027; compliance generally not expected with other QS requirements (except for complaint files)	compliance generally not expected
Non-molecular antisera LDTs for rare red blood cell antigens	compliance generally expected beginning May 6, 2025	compliance generally expected beginning May 6, 2026	compliance with 21 CFR 820.180-820.186 generally expected beginning May 6, 2027; compliance generally not expected with other QS requirements (except for complaint files)	compliance generally not expected
LDTs approved by NYS CLEP	compliance generally expected beginning May 6, 2025	compliance generally expected beginning May 6, 2026	compliance generally expected beginning May 6, 2027	compliance generally not expected
Modified version of another manufacturer’s 510(k) cleared or De Novo authorized test within the scope described in the preamble	compliance generally expected beginning May 6, 2025	compliance generally expected beginning May 6, 2026	compliance generally expected beginning May 6, 2027	compliance generally not expected
IVDs offered as LDTs within scope of phaseout policy, but that do not fall within a targeted enforcement discretion policy summarized above	compliance generally expected beginning May 6, 2025	compliance generally expected beginning May 6, 2026	compliance generally expected beginning May 6, 2027	compliance generally expected beginning November 6, 2027 for high-risk tests compliance generally expected beginning May 6, 2028 for moderate-risk and low-risk tests

FDA’s LDT final rule finalized a policy under which FDA will phase out its general enforcement discretion approach for LDTs over the course of four years so that IVDs manufactured by a laboratory will generally fall under the same enforcement approach as other IVDs. The phaseout includes targeted enforcement discretion policies for specific categories of IVDs manufactured by laboratories.

The SECG comes after FDA updated last week its LDT website to reflect the planned dates on which FDA will phase out enforcement discretion for the tests, thus setting into motion the agency’s plan to begin regulating the products. On May 6 of each of the following years (except for Stage 4), the corresponding stages will begin as the Phaseout policy:

Stage 1: On May 6, 2025 (one year after publication of the final rule), FDA will begin to enforce the requirement under 21 CFR 820.198 for complaint files which will serves an and input for medical device reporting (MDRs) and correction and removal reporting on LDTs, as well as complaint record keeping.
Stage 2: In 2026 (two years after publication of the final rule), FDA will begin to enforce additional medical device requirements on LDTs, including registration and listing, labeling, and investigational use requirements.
Stage 3: In 2027 (three years after publication of the final rule), FDA will begin enforcing the rest of the amended Quality System Regulation (21 CFR Part 820) on LDTs (other than those on complaints as an input to MDR, which are imposed in Stage 1) with a heavy emphasis on design controls.
Stage 4: On November 6, 2027 (three and a half years after publication of the final rule), FDA will begin to apply premarket review requirements for high-risk IVDs offered as LDTs, meaning those that may be classified as Class III devices or biologics requiring licensure and where an application has been submitted before November 6, 2027, the agency will continue its enforcement discretion while it reviews the application. Notably, marketed high-risk IVDs offered as LDTs that file a PMA before the start of Stage 4 will be able to continue marketing their tests while the marketing application is pending.
Stage 5: On May 6, 2028 (four years after publication of the final rule), FDA will stop using enforcement discretion for moderate-risk and low-risk IVDs offered as LDTs, meaning those that require premarket submissions and will similarly continue to exercise enforcement discretion for applications submitted before May 6, 2028 while it review the application.

FDA’s LDT final rule will become effective on July 5, 2024, unless parties opposed to FDA’s plan successfully sue to invalidate the agency’s rulemaking (see one such lawsuit discussed online here).