FDA Finalizes LDT Regulation; Partial “Grandfather” Exemptions for Existing LDTs

FDA Finalizes LDT Regulation; Partial “Grandfather” Exemptions for Existing LDTs

FDA Finalizes LDT Regulation; Partial “Grandfather” Exemptions for Existing LDTs

Although less severe than the FDA’s initial proposed regulations, the Final Rule (published May 6) will add a new complex layer of bureaucracy for labs offering laboratory-developed tests (LDTs). LDTs on the market prior to May 6 will not have to go through the full FDA application and clearance process. However, labs will need to develop quality system complaint files, registration, labeling, etc. for each LDT they currently offer. New LDTs will ultimately need to go through the full FDA application and
clearance process.

Jonathan Genzen, MD, PhD, Chief Medical Officer and Senior Director of Governmental Affairs at ARUP Laboratories (Salt Lake City, UT), has been closely following the FDA’s movement toward regulating laboratory developed tests. Below we summarize Dr. Genzen’s perspectives on the Final Rule with an emphasis on what it means for currently marketed LDTs. 

What are the Stage 1 requirements for “grandfathered” LDTs under the Final Rule?

These tests are not fully “grandfathered” under the Final Rule, as certain FDA oversight requirements still apply.

Currently marketed LDTs (on the market prior to May 6, 2024) will need to comply with FDA Medical Device Reporting (MDR) regulations. This includes reporting certain device-related adverse events and product problems to the FDA, as well as correction and removal reporting requirements.

Currently marketed LDTs will also need to comply with one of the Stage 3 quality system requirements (Complaint Files — 21 C.F.R. 820.198). Laboratories will be required to establish and maintain procedures for receiving, reviewing, and evaluating complaints for their LDTs.

The Stage 1 requirements will need to be met by May 6, 2025.

What are the Stage 2 requirements for “grandfathered” LDTs under the Final Rule?

Currently marketed LDTs will need to comply with FDA registration, listing, labeling, and investigational use requirements by May 6, 2026. The most complex of these requirements is labeling. It appears that all LDTs eligible under the currently marketed enforcement discretion policy will need to meet full FDA labeling requirements for IVDs. This will be a complex task to conduct retrospectively, as labeling requirements are extensive and will need to be completed within two years to remain in compliance with the Final Rule.

Which anatomic pathology services are covered under the Final Rule for LDTs?

From my interpretation, with the exception of manual staining and manual immunohistochemistry (“1976-type” LDTs), the Final Rule doesn’t distinguish between AP and CP testing. The Final Rule appears to apply to all LDTs, with the exception of manual interpretation of the final slides by a pathologist. This means that currently performed anatomic pathology LDTs, including non-manual IHC staining, are now subject to FDA oversight.

What happens when an existing LDT is modified?
The moment a currently marketed test has a modification considered to be significant by the FDA (and they provide representative examples in the Final Rule), then the LDT would be subject to additional QS requirements including design controls, purchasing controls, acceptance activities, corrective and preventive action (CAPA), and records requirements. Such  modifications to existing LDTs will also require a premarket submission to the FDA.

Over time, I anticipate that many routine test modifications, including sample type changes and automation of manual assays on liquid handlers, will now necessitate FDA submissions. And I suspect that the FDA is underestimating the number of tests that will ultimately need to go through premarket review, as well as the financial impact to the clinical laboratory community.

Is the NYS CLEP less expensive and a quicker process than FDA review?

I believe that LDT submission and review under the NYS Clinical Laboratory  Evaluation Program (CLEP) – which oversees clinical laboratory testing for NY patients – is available only to NYS-accredited labs. NY clinical laboratory accreditation is likely not a practical option for most laboratories that do not intend to perform testing on NY patients. The NY CLEP performs outstanding, high-quality work, and they will need to share their perspective on how the program should or should not be used in the context of the FDA’s Final Rule.

Is a lawsuit challenging FDA’s authority to regulate LDTs likely?
I believe that litigation is very likely. The FDA’s language in the Final Rule regarding “illegality” (page 30) makes this even more likely in my opinion. If not following the FDA’s new framework for LDTs is deemed illegal—even if it compromises the ability to care for patients (e.g. emergency validations for clinically urgent testing in acute settings) – then the lab industry has been backed into a corner and judicial review could be the only remaining remedy.

FDA Finalizes LDT Regulation; Partial “Grandfather” Exemptions for Existing LDTs

FDA Final LDT Rule Could be Published Soon

FDA Final LDT Rule Could be Published Soon

On March 1, the FDA submitted its final rule for LDT regulation to 
the White House’s Office of Information and Regulatory Affairs 
(OIRA). This is a perfunctory last step before the final rule is published
in the Federal Register. This could occur as soon as April 1. This will be
the most impactful new regulatory change for laboratories since PAMA
completely overhauled the Medicare CLFS in 2018.


OIRA (pronounced “oh-eye-rah”) is a statutory part of the Office of Management and Budget within the Executive Office of the President. OIRA is responsible for reviewing all federal regulations (i.e., the Executive Branch’s administrative actions) to ensure they meet all statutory requirements. OIRA is currently headed by Richard Revesz, Administrator, who was appointed by President Biden and confirmed by the U.S. Senate in late 2022.

“OIRA reviewed the proposed rule in record time, so it is reasonable to expect that the review of the final rule will not be protracted. I would not be surprised if OIRA completes its review in 30 days and FDA publishes the final rule in the federal register in the first week of April,” according to attorney Sheila Walcoff, Chief Executive at the IVD consulting firm Goldbug Strategies (Gaithersburg, MD).

Typically, a final rule will specify an effective date of 30 or 60 days after the publication date, adds Walcoff.

Once a final rule is published it will be difficult to overturn.

Last Chance to Sway OIRA Against Regulation 

OIRA staff held nine teleconferences with organizations advocating both for and against FDA LDT regulation last year. OIRA is next scheduled to meet with The Association for Diagnostics and Laboratory Medicine (ADLM — formerly AACC) on March 18. ADLM, which represents approximately 8,000 members, including clinical labs and IVD manufacturers, has steadfastly
opposed FDA regulation of LDTs. This could be the last chance that the lab industry has to sway OIRA against rubber-stamping the final rule.

Expected Legal Challenge

A final rule is almost guaranteed to trigger a lawsuit from lab trade groups, which will argue that the FDA does not have the authority to regulate LDTs.
The American Clinical Laboratory Assn. (ACLA — Washington, DC) seems to be gearing up for a lawsuit to the impending final rule. In a statement, ACLA President Susan Van Meter said:

ACLA has significant concerns about the legality and impact of FDA unilaterally imposing an ill-fitting medical device scheme on laboratory-developed testing services, which are professional services and not medical products. Should the agency promulgate a final rule, ACLA will assess its options at that time; but we continue to urge the agency to withdraw the proposed rule and reengage on advancing appropriate legislation.

Could a New Trump Administration Put the Kibosh on LDT Regulation?

As a component of OMB, OIRA is part of the Executive Office of the President and helps ensure that covered agencies’ rules reflect the President’s policies and priorities.

The FDA is moving quickly because the national election in November could result in a new administration opposed to LDT regulation. A new President could, immediately upon taking office, prevent a proposed rule from being finalized, according to long-time lab regulation expert Dennis
Weissman (Falls Church, VA).

However, Weissman says that changing or canceling a final rule is much more difficult. Once a federal rule has been finalized a new administration would be required to undergo the formal rulemaking process (i.e., opportunity for public comment on a proposal followed by final rule) to change or repeal all or part of a final rule.

In addition to this administrative action, Congress could also take legislative action to overturn a final rule, notes Weissman.


FDA Won’t Extend Comment Period on LDT Regs

FDA Won’t Extend Comment Period on LDT Regs

FDA Won’t Extend Comment Period on LDT Regs

The FDA has announced that its standard 60-day comment period for its proposed regulation of laboratory-developed test (LDTs) will not be extended past December 4. Several trade groups, including CAP and ACLA, had requested to stretch the comment period to 120 days. An extension would have potentially delayed implementation of the rule while giving Congress more time to pass LDT reform legislation. The FDA has indicated that a final rule could be published as early as April 1, 2024.

The FDA estimates that there are approximately 12,000 U.S. labs performing high-complexity testing and that 10% of these are marketing LDTs. These 1,200 labs are currently offering 80,400 LDTs and 7,776 new LDTs are coming to the market each year. The FDA estimates that labs will generate $28.6 billion of revenue from LDTs in 2023.

One of the biggest concerns is the FDA’s capacity to review and process as many as 80,000+ LDT applications over the next few years. For example, the FDA gave marketing authorization to a grand total of only 765 medical devices, including lab tests, in 2022, according to the FDA’s Center for Devices and Radiological Health 2022 Annual Report. The FDA’s ability to process tens of thousands of LDT applications in a timely manner, even with the help of third-party reviewers, is doubtful.

During an October 24 call with investors, Jim Davis, Chief Executive of Quest Diagnostics, said that Quest agrees with the long-standing assertion of the American Clinical Laboratory Assn. (ACLA), “that the FDA does not have the statutory authority to unilaterally regulate LDTs under its existing medical device authority.” Davis noted that by volume, LDTs account for less than 10% of Quest’s overall testing business. Quest performs the majority of its LDT testing at three ISO-certified labs, including San Juan Capistrano, CA; Chantilly, VA; and Lewisville, TX.

On an October 26 conference call, Labcorp CEO Adam Schechter said that LDTs account for less than 5% of Labcorp’s volume and less than 10% of its testing revenue. “If you look at the rigor that we go through with our laboratory-developed tests, we think we do the vast majority of what they [FDA] would be asking for anyway.” Schechter said FDA regulation could have unintended consequences. LDTs “are sometimes the most important test for new specialty areas. And getting those tests to patients quickly is what’s most important.”

One group in favor of LDT regulation is AdvaMed (Washington, DC), whose members include Abbott, BD, Bio-Rad Laboratories, bioMerieux, Hologic, Illumina and Roche. “We like the rule….This is really about making sure there’s a level playing field when you’re talking about diagnostics tests and having everything go through a similar pathway,” said AdvaMed CEO Scott Whitaker at an October 10 press conference. “Either you raise the regulatory standard, or you lower the regulatory standard, but you do it across the board without stifling innovation,” he said.

The last major effort by the FDA to formally regulate LDTs came in October 2014, when the agency issued draft guidance. But after collecting comments and facing two years of stiff opposition, the agency chose not to issue final guidance. One of the strongest critics was ACLA, which challenged the FDA’s authority over the tests by filing a citizen petition and making clear its intent to sue if necessary.