The FDA’s final rule for regulation of lab-developed tests (LDTs) is likely to remain controversial for the foreseeable future, although Congress can still put those controversies to rest. In the absence of legislation, however, clinical labs will soon be subject to an entirely new set of regulatory requirements, drastically elevating the compliance risks for the operators of these labs.
Four-year Phase-in of Rule’s Requirements
Labs will still be subject to CLIA regulation even with the FDA final rule in place, but compliance operations will quickly grow more complex. The timelines as described in the final rule are:
- After one year (as of May 6, 2025), labs must be in compliance with FDA requirements for medical device reporting, reports of corrections and removals, and complaint handling.
- After two years (May 6, 2026), labs will be subject to establishment registration and listing requirements as well as requirements for labeling and investigational test uses.
- After three years (May 6, 2027), labs must be compliant with the Quality Management System Regulation (QMSR), which the agency finalized in January 2024.
- After three-and-half years (Nov. 5, 2027), developers of high-risk in vitro diagnostic (IVD) tests must have FDA approval, although the agency will exercise enforcement discretion for tests when the agency is in receipt of an application.
- After four years (May 6, 2028), premarket review requirements for moderate- and low-risk IVDs will be in effect, although again, pending applications may be granted enforcement discretion.
One of the key elements of the final rule is the enforcement discretion policy for LDTs that had been marketed prior to the date of the final rule. These tests will be subject to requirements for MDRs and complaint-handling practices, but will not be subject to the requirements of the QMSR or premarket review requirements. However, the test developer cannot significantly modify the test and expect to sustain this discretion.
‘Any tests reviewed by the clinical lab evaluation program run by the New York State Department of Health would be eligible for enforcement discretion as well’
The FDA also offers enforcement discretion for LDTs administered for an unmet need, assuming the test is performed in the healthcare system in which the patient is receiving care. Any tests reviewed by the clinical lab evaluation program run by the New York State Department of Health would be eligible for enforcement discretion for premarket review, while tests for drug enforcement and tests run in labs operated by the Department of Veterans Affairs would enjoy nearly unlimited enforcement discretion.
Potential Legal and Congressional Challenges
We previously blogged on the question of the draft rule, highlighting the issue of whether the FDA possesses the statutory authority to undertake rulemaking. One trade association has already filed suit to block the final rule, while two other organizations (here and here) have criticized the final rule as an example of regulatory overreach. The lawsuit by the American Clinical Laboratory Association (ACLA) argues that LDTs are professional services rather than regulated devices, and that CLIA, which has been amended on several occasions since 1988, is sufficient to ensure the quality and reliability of LDTs. The demise of Chevron deference is likely to strengthen the ACLA’s suit in the minds of many, including former FDA Commissioner Scott Gottlieb.
The ACLA lawsuit may or may not run its course by the end of CY 2024, but a change in administration at the White House could lead to a withdrawal of the final rule. This would be a much more drawn-out process than withdrawal of sub-regulatory guidance, however, as withdrawal of a rule must be conducted under the terms of the Administrative Procedure Act.
Because the final rule was passed prior to the final 60 days of the current administration’s term, Congress cannot leverage the Congressional Review Act to overturn the rule. Two members of the House of Representatives have called on Congress to pass the Verifying Accurate, Leading-edge IVCT Development (VALID) Act in response to the FDA final rule, although it is not clear that the prospects for legislation are particularly good in this general election year.
The FDA posted two draft guidances in connection with the LDT final rule, one of which is for prescription use-only tests produced in immediate response to chemical, biological, radiological or nuclear (CBRN) threats. This draft covers such considerations in the absence of the issuance of a public health emergency declaration under Section 564 of the Food Drug and Cosmetic Act. In order for tests to fall under the scope of this draft guidance, the lab would have to validate the test and notify the FDA of its use.
These immediate-response tests would be those deployed immediately after detection of an outbreak and before either the resolution of the outbreak or a declaration under Section 564. However, tests that use home collection kits would not be eligible, nor would at-home tests.
The second draft guidance applies when a public health emergency has been declared under Section 564, which is separate from the agency’s emergency use authorization (EUA) authority. Several factors would be considered in the decision whether to issue an enforcement discretion policy under this guidance, such as the rate of disease transmission, the potential for asymptomatic infection, and the size of the population that may have been exposed to the CBRN threat. The FDA will consider the lab’s experience with test development in similar circumstances, so long as the agency has no compliance concerns regarding that lab. However, the FDA said it would expect to receive a submission under the EUA program within a reasonable amount of time.
This final FDA rule will be exceptionally disruptive to the operations of clinical labs, so it may be prudent for labs to begin working toward compliance. Some of the features of the FDA rule are reflected in the VALID Act, however, such as the FDA’s authority to conduct inspections and the requirement for premarket applications. While preparing for a compliance regime that never comes into force may seem a pointless expense, a failure to prepare for a compliance regime that is instituted is by far the bigger risk for the operator of a clinical lab.
