The Food and Drug Administration issued a long-awaited
proposed rule on Sept. 29 that would establish a regulatory framework for laboratory-developed tests (LDTs).
FDA proposes to modify the definition of in vitro diagnostic products (IVDs) to explicitly include IVDs manufactured by laboratories. FDA generally considers a LDT to be “an IVD that is intended for clinical use and that is designed, manufactured, and used within a single laboratory that is certified under the Clinical Laboratory Improvement Amendments [CLIA] of 1988 and meets the regulatory requirements of CLIA to perform high-complexity testing.” Since IVDs are devices, LDTs would be classified and regulated as devices.
FDA provides that until now, it has exercised enforcement discretion and has not enforced applicable requirements with respect to most LDTs. FDA proposes to phase out its general enforcement discretion approach for LDTs so they generally fall under the same enforcement approach as other IVDs. However, enforcement discretion would continue for specified LDTs. FDA also clarifies that its enforcement discretion approach for LDTs has never applied to certain types of tests:
- Blood donor screening tests and human cells, tissues, and tissue-based products (HCT/P) donor screening tests required under 21 CFR 610.40 and 21 CFR 1271.80(c), and tests for the determination of blood group and Rh factors required under 21 CFR 640.5 do not fall within the scope of the proposed rule. FDA specifies that the agency’s general enforcement discretion approach for LDTs has never applied to donor screening tests that are required for infectious disease testing or for detection of blood group and Rh factors, since these tests are critical for ensuring the safety of blood and blood components and HCT/Ps and incompatible blood transfusions. A blood or HCT/P establishment must not use a test for the purposes listed unless the test is licensed, approved, or cleared by FDA for such use. Blood and HCT/P establishments must register with FDA, are subject to FDA inspection, and generally comply with the regulatory requirements related to these tests.
- Similarly, human leukocyte antigen (HLA) tests used for blood transfusions are not subject to the proposed rule. While FDA will continue to enforce applicable requirements for HLA tests used for blood transfusions, the general enforcement discretion approach does not apply to these tests.
- FDA proposes to continue exercising enforcement discretion for HLA tests "that are designed, manufactured, and used in a single laboratory certified under CLIA that meets the requirements to perform high-complexity histocompatibility testing when used in connection with organ, stem cell, and tissue transplantation to perform HLA allele typing, for HLA antibody screening and monitoring, or for conducting real and ‘virtual’ HLA crossmatch tests.” FDA reasons that “HLA LDTs for transplantation used in histocompatibility laboratories that meet the regulatory requirements under CLIA to perform high complexity testing, when used in connection with organ, stem cell and tissue transplantation for certain purposes as described in this paragraph, are unique in that they are generally developed, and the testing is generally performed, in urgent, life-saving situations for the patient.”
- FDA proposes to continue to exercise general enforcement discretion for "1976-Type LDTs," which include: "use of manual techniques (without automation) performed by laboratory personnel with specialized expertise; use of components legally marketed for clinical use; and design, manufacture, and use within a single CLIA-certified laboratory that meets the requirements under CLIA for high complexity testing." An example of these tests includes immunohistochemistry tests that involve no automated preparation or interpretation.
- FDA proposes to continue its longstanding approach to exercise enforcement discretion for tests intended solely for forensic (law enforcement) purposes, which applies to such tests regardless of whether they are offered as an LDT.
FDA is soliciting comments on how to define academic medical center (AMC) laboratories, since these laboratories may operate differently than others. The agency is considering whether it should have a different policy for AMC laboratories. FDA suggests that possible criteria that would describe an AMC laboratory may include:
- A laboratory for which a certificate is in effect under CLIA and that meets the requirements under CLIA to perform tests of high complexity;
- That is part of an accredited public or nonprofit private AMC that has a medical residency training program or fellowship program related to test development, application and interpretation; and
- That is integrated into the direct medical care for a patient, including specimen collection, testing, interaction with the treating provider, and, as appropriate, patient treatment based on the test, all at the same physical location.
FDA intends to publish a final phase-out policy in the preamble to the final rule. FDA proposes a five-stage approach to phasing out enforcement discretion for most LDTs, so they would generally fall under the same enforcement approach as other IVDs:
- Stage 1: End the general enforcement discretion approach with respect to medical device report (MDR) requirements and correction and removal reporting requirements one year after FDA publishes the final phase-out policy.
- Stage 2: End the general enforcement discretion approach with respect to requirements besides MDR, correction and removal reporting, quality systems (QS), and premarket review requirements two years after FDA publishes the final phase-out policy.
- Stage 3: End the general enforcement discretion approach with respect to QS requirements three years after FDA publishes the final phase-out policy.
- Stage 4: End the general enforcement discretion approach with respect to premarket review requirements for high-risk IVDs 3.5 years after FDA publishes the final phase-out policy, but not before Oct. 1, 2027.
- Stage 5: End the general enforcement discretion approach with respect to premarket review requirements for moderate risk and low risk IVDs (that require premarket submissions) four years after FDA publishes the final phase-out policy, but not before April 1, 2028.
AABB is interested in receiving feedback on tests and testing methods that may still be captured as LDTs and subject to the device regulatory paradigm outlined in the proposed rule. Specifically, AABB is interested in learning which LDT methods are in place and examples of where that testing is currently used. Please send this information, questions or requests for additional information to AABB at
regulatory@aabb.org.
