FDA laboratory developed tests: FDA’s final rule on LDTs and what this means for laboratories

Christine P. Bump Date published: Jul 09, 24

On May 6, 2024, the US Food and Drug Administration (FDA) published its final rule to regulate laboratory developed tests (LDTs) as medical devices. The FDA lab developed test rule amends the definition of in vitro diagnostic (IVD) devices to include tests that are manufactured in a laboratory, which eliminates the legal and regulatory distinction between IVDs and LDTs.

Thus, laboratories and the tests they develop must comply with FDA’s regulations and requirements for devices. The most burdensome of the FDA lab developed test requirements is the premarket review process, which generally requires manufacturers to submit 510(k) clearance, De Novo authorization or Premarket Approval (PMA) applications for FDA’s review before a device can be marketed.

Laboratories are already regulated by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments (CLIA). The FDA laboratory developed test final rule does not replace CLIA. Rather, laboratories will have to comply with CLIA requirements and FDA’s device regulations, as well as requirements and certifications under accreditation bodies –  such as the College of American Pathologists (CAP) and the International Organization for Standardization (ISO).

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How will FDA enforce its device regulations?

FDA asserts that it has long had authority over LDTs, but has been exercising “enforcement discretion.” The agency recognizes that most laboratories are not familiar with its regulations and requirements. The final rule for FDA lab developed tests therefore includes a five-stage policy under which FDA will phase out its enforcement discretion for LDTs:

• Stage 1: By May 6, 2025, laboratories must comply with FDA lab developed test regulations for medical device reporting, corrections and removals reporting and complaint files.
• Stage 2: By May 6, 2026, laboratories must comply with FDA lab developed test regulations for facility registration and product listing, labeling and investigational uses of devices.
• Stage 3: By May 6, 2027, laboratories must comply with FDA’s quality system requirements for design controls, purchasing controls, acceptance activities, corrective and preventative actions and records.
• Stage 4: By November 6, 2027, laboratories must submit PMAs for high-risk tests.
• Stage 5: By May 6, 2028, laboratories must submit 510(k)s or De Novos for moderate-risk tests.
  
  

Some tests are exempt from one or more stages of the phaseout policy

Though many lab developed tests will be subject to all stages of the phaseout policy, LDTs that meet certain criteria may be exempt from part or all of the policy. Under the final rule:

Four types of tests are exempt from the phaseout policy entirely. For these tests, FDA will continue to exercise enforcement discretion for all device regulations and requirements:

• “1976-Type LDTs” which, among other criteria, do not use automation
• HLA tests for transplantation, as defined in the final rule
• Tests intended solely for law enforcement purposes
• LDTs manufactured and performed within the Department of Defense or Veteran’s Health Administration

Two types of tests are exempt from premarket review requirements under Stages 4 and 5 of the phaseout policy. All requirements under Stages 1, 2 and 3 apply:

• LDTs approved by the New York State Department of Health Clinical Laboratory Evaluation Program
• Modified versions of another manufacturer’s 510(k)-cleared or De Novo-authorized test, if the modifications comply with requirements under the final rule

Three types of lab developed test are exempt from premarket review requirements under Stages 4 and 5 of the phaseout policy and the quality system requirements under Stage 3, except for records. These tests must comply with Stages 1 and 2, and the records requirements under Stage 3:

• “Currently marketed LDTs,” which were on the market on May 6, 2024, and are not modified in a “significant” way (as described in the final rule)
• LDTs for “unmet needs” that are developed and offered in an integrated health system (meaning the laboratory and patient’s physicians are within the same corporate entity)
• Non-molecular antisera LDTs for RBC antigens for transfusion compatibility, as defined in the final rule.

These exemptions from one or more stages of the FDA LDT phaseout policy will end if a test no longer meets all of the required criteria under the final rule. For example, if a test previously used solely for law enforcement purposes is used for diagnostic or treatment purposes, the test will be subject to all five stages of the phaseout policy. Additionally, any lab developed test developed after May 6, 2024, but before the end of the phaseout policy, must comply with all stages of the FDA LDT phaseout policy unless an exemption applies to the test.

When will the FDA lab developed test final rule be implemented?

The final rule takes effect on July 5, 2024, but the clock to comply with the phaseout policy began on May 6. Many stakeholders oppose one or more aspects of the final rule, and there are four ways that the rule could be nullified, repealed or rescinded.

• On May 15, 2024, a joint resolution to nullify the final rule was introduced in Congress, under the Congressional Review Act. If President Biden signs the resolution by July 5, the rule would be nullified. That is unlikely.
• The American Clinical Laboratory Association filed a lawsuit against FDA on May 29, 2024, in the US District Court for the Eastern District of Texas. The lawsuit requests the court enter a declaratory judgment that FDA is not authorized to regulate LDTs as devices and stop FDA from enforcing the final rule. Courts in Texas are not favorable to FDA, so it will be interesting to see how this case proceeds.
• Congress may introduce legislation that creates a less burdensome regulatory framework for laboratory developed tests. New legislation can repeal an agency rule or regulation.
• Under a new presidential administration, FDA could rescind the final rule by proposing a new rule that justifies why the FDA LDT final rule should be rescinded.
  
  

What should laboratories do now to prepare for the FDA laboratory developed test final rule?

Despite pending efforts to nullify, repeal or rescind the final rule, laboratories should assume it will be fully implemented and enforced. Any successful legal or legislative action is not likely to take effect until after the deadlines for Stages 1 and 2 and perhaps 3, of the phaseout policy. Therefore, laboratories should now:

• Determine whether their lab developed tests fall under any category of continuing enforcement discretion.
• Understand FDA’s LDT regulations and requirements under at least Stage 1 of the phaseout policy.
• Develop and implement systems and processes to comply with at least Stage 1, unless tests are exempt from the phaseout policy entirely.
• Identify budget options and possible funding sources to prepare for the increased costs to comply with FDA’s device regulations.

FDA’s device regulations have operational and administrative requirements that differ from those under CLIA or ISO. Moreover, FDA, CLIA and ISO have separate and distinct standards for test development, methodology and validation. Laboratories must therefore ensure that they fully understand the FDA lab developed test final rule and FDA’s device regulations and requirements.

Failure to comply with any aspect of FDA’s regulations can cause a test to lose an exemption under the final rule’s phaseout policy. FDA can also pull tests from the market and stop laboratories from operating.

To help to ensure compliance, laboratories may need to hire new employees or retain consultants or legal counsel with knowledge of and experience with FDA regulations. Laboratories may also benefit from tools that maintain compliance, including effective quality management systems.

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