On April 29, 2024, the Food and Drug Administration (FDA) announced a Final Rule amending regulations to make explicit that in vitro diagnostic products (IVDs) are devices under the Federal Food, Drug, and Cosmetic Act including when the manufacturer of the IVD is a laboratory. Under the new rule, the FDA will phase out its laboratory developed test (LDT) enforcement discretion policy over a four-year period. The phaseout policy “applies to IVDs that are manufactured and offered as LDTs by laboratories that are certified under CLIA[1] and that meet the regulatory requirements under CLIA to perform high complexity testing, and used within such laboratories, even if those IVDs do not fall within FDA’s traditional understanding of an LDT because they are not designed, manufactured, and used within a single laboratory.”

IVDs are intended for use in the collection, preparation and examination of specimens taken from the human body such as blood, saliva or tissue. IVDs measure or detect substances, analytes, or markers in the body, such as proteins, sodium, cholesterol, or DNA. The FDA defines LDTs as IVDs “intended for clinical use and are designed, manufactured, and used within a single laboratory that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA)[2] and meets the regulatory requirements under CLIA to perform high complexity testing.” The FDA has exercised enforcement discretion for most LDTs which means they have not undergone FDA premarket review, and therefore, clinical validity has not been established.

Sophisticated technology, global expansion, and increases in cybersecurity issues have made the risks associated with modern LTDs greater than the risks associated with LTDs used decades ago. According to the FDA, changes in business practices and the increasing ability to ship specimens across the country quickly allow LDTs to be used for a larger and more diverse population and are used more frequently when making critical health care decisions. After years of discussions regarding increased oversight of LDTs, FDA is now phasing out discretionary enforcement, with some exceptions.

The four-year phaseout period contains five stages with Stage 1 beginning on May 6, 2025.

• Stage 1: beginning one year after the publication date of the final rule, or IVDs offered as LDTs, FDA will expect compliance with MDR requirements, correction and removal reporting requirements, and QS requirements under § 820.198 (complaint files).
• Stage 2: beginning two years after the publication date of the final rule, for IVDs offered as LDTs, FDA will expect compliance with requirements not covered during other stages of the phaseout policy, including registration and listing, labeling, and investigational use requirements.
• Stage 3: beginning three years after the publication date of the final rule, for IVDs offered as LDTs, FDA will expect compliance with QS requirements other than complaint files addressed in Stage 1.
• Stage 4: beginning three and a half years after the publication date of the final rule, FDA will expect compliance with premarket review requirements for high-risk IVDs offered as LDTs.
• Stage 5: beginning four years after the publication date of the final rule, FDA will expect compliance with premarket review requirements for moderate-risk and low-risk IVDs offered as LDTs (that require premarket submissions).

At the end of the phaseout period, the FDA will no longer have general enforcement discretion for LDTs, while maintaining targeted enforcement discretion for a number of categories of IVDs including:

• LDTs manufactured and performed by a laboratory integrated within a healthcare system to meet an unmet need of patients receiving care within the same healthcare system.
• LTDs unlikely to pose significant risks or are conducted in circumstances that themselves will mitigate the risks.
• Currently marketed IVDs offered as LDTs that were first marketed prior to the date of issuance of this rule and that are not modified, or that are modified in certain limited ways.

The Final Rule will become effective on July 5, 2024.

[1] The Clinical Laboratory Improvement Amendments (CLIA) program regulates laboratories that perform testing on patient specimens in order to ensure accurate and reliable test results.

[2] Under the CLIA regulations, when a laboratory uses a test system that has not received FDA clearance or approval, the laboratory may not release any test results prior to establishing certain performance characteristics relating to analytical validity for the use of that test system in the laboratory’s own environment.

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