At a Glance
- FDA’s new rule on lab-developed tests (LDTs) faces opposition due to concerns over patient access and test development costs;
- College of American Pathologists (CAP) advocates for FDA oversight of only high-risk LDTs, arguing most can be regulated using existing Quality methods; and
- The industry awaits the new administration’s stance on the LDT rule, with compliance deadline approaching on 06 MAY 2025.
As Donald Karcher, MD, FCAP, President of the College of American Pathologists (CAP) sees it, not all laboratory-developed tests (LDTs) are created equally. “There are clearly varying degrees of risk to these tests,” he told MD+DI.
On the low-risk side of the spectrum are LDTs such as histochemical tests, which typically use dyes on skin cells and tissue to assist in disease diagnosis, and molecular tests that utilize polymerase chain reaction methodology to analyze blood, tissue, and urine. From a high-risk standpoint, there are those that contain proprietary algorithms for use in a single lab and for which there is no opportunity to conduct proficiency testing or external verification of accuracy and validity.
With such an inherent variance among LDTs, Karcher, the CAP, and other advocacy groups are continuing to call for the repeal of the final rule issued by the United States Food and Drug Administration (FDA) last April (2024) that amended a regulation to bring LDT oversight away from the Centers for Medicare and Medicaid Services (CMS) and under the jurisdiction of FDA. A phased enforcement approach is slated to begin 06 MAY 2025.
A changing of the guard in the White House this year is providing some glimpse of optimism among those who oppose the ruling that the new governance of LDTs can end before it officially begins; however, as Karcher also explained, any degree of positivity currently all comes down to one’s perspective on how to read the tea leaves from the new administration’s early approach to current policy.
Gleaning intent of executive orders
On the heels of an Executive Order signed by President Trump in late January 2025, Karcher wrote a letter on behalf of CAP’s members to newly appointed Health and Human Services Secretary, Robert F. Kennedy, Jr., in February 2025 that asks for FDA rulemaking to be rescinded.
A central component to CAP’s stance on the potential of the current administration to heed their call stems from the January 2025 Executive Order Unleashing Prosperity Through Deregulation, which, in part, states a purpose to “…ensure that the cost of planned regulations is responsibly managed and controlled through a rigorous regulatory budgeting process…” and to “…alleviate unnecessary regulatory burdens placed on the American people…”
This premise offers a recent precedent to assume that repeal is a realistic option,” said Karcher. “[The administration] appears to be in favor of removing regulation, particularly regulation that is disruptive or overly costly,” he said.
In his letter dated 14 FEB 2025, Karcher wrote that the CAP is “…concerned about the FDA rule for several reasons – most importantly because of its impact on patient access to critically important diagnostic tests, the timeline for implementation, it may not address the intent of improving patient safety, and the unsustainable costs to laboratories that will hinder the development of LDTs…”
While Karcher and the CAP are not opposed to FDA regulating the highest-risk LDTs, that is where they believe its oversight should begin and end due to a lack of an appropriate framework for the regulation of the variety that defines LDTs overall. “The CAP still believes that the FDA is the right Agency to regulate the highest-risk LDTs,” Karcher said. “We define that group as those so-called ‘black box tests’ that are using proprietary algorithms, that are not transparent, where there is no proficiency testing that can be done. We feel that kind of regulation is good for patients. However, we feel that high-risk LDTs are a very small percentage of all LDTs. And we feel that all other LDTs can be regulated by basically using the same methods that we have used for decades to develop good, quality, accurate, appropriate, and properly validated LDTs.”
According to Michele L. Buenafe, a Partner at Morgan Lewis, a multinational law firm that provides strategic counseling to in vitro diagnostics manufacturers and clinical laboratories, there is at least potential that the executive order could impact the ruling on LDTs. “Potentially, this Executive Order could impact the LDT final rule if incoming FDA leadership decides that actively regulating LDTs is not consistent with the new administration’s priorities or the costs and burdens to private industry outweigh any potential benefits.”
Buenafe also suggests that the rule could have already come under review per the executive order Regulatory Freeze Pending Review which was issued 20 JAN 2025. “Under that Executive Order, federal agencies were directed to consider postponing for 60 days any published or issued rules that ‘have not taken effect, for the purpose of reviewing any questions of fact, law, and policy that the rules may raise,’” said Buenafe. “Agencies may consider reopening comments during this 60-day period ‘where appropriate and consistent with applicable law’ or further delay implementation of such rules beyond the 60-day if needed to continue the review.” With this window ended 21 MAR 2025, any potential updates would have been made known at that time.
Need for a foundational framework
The history of medical device regulation in the U.S. is a bit complicated. A public push for more oversight of devices in the 1960s and 1970s led to the Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act in 1976, which established the Regulatory pathways for new devices to get to market, i.e. premarket approval (PMA process) and premarket notification [510(k) process].
In 1988, the Clinical Laboratory Improvement Amendments (CLIA) overseen by CMS established federal standards to ensure the quality and accuracy of clinical laboratory testing, regardless of where the test is performed, and provided the authority for certification and oversight of clinical laboratories.
In September 2014, the FDA proposed a framework for regulating LDTs; however, drafted guidance was never finalized and so its historical relationship with LDTs has been one of enforcement discretion.
In 2021, the Verifying Accurate, Leading-edge IVCT Development (VALID) Act was submitted to Congress after its introduction in 2020 and having since been revised several times without being passed. Among those groups that supported the VALID Act was the CAP. “We worked for four years with Congress and FDA to try to make the VALID Act acceptable,” said Karcher. “And FDA was very clear that if legislation was not passed, if Congress did not provide the appropriate framework, they felt that they had no choice but to regulate LDTs based on their existing statutory authority – and that’s exactly what they did. The result of this has been predictable – the framework under their existing statutory authority was never the right framework. And they did that because they felt they had no choice. And we have opposed the proposed rule and the final rule every step of the way.”
There are several reasons for the opposition to FDA final rule, said Karcher. “It’s overly costly, it’s overly burdensome for labs, it will stop labs from developing LDTs, and therefore we feel that it should not go forward,” he said. “As it stands, the rule requires labs to go through multiple regulatory steps. It therefore becomes very expensive for laboratories to develop LDTs. The concern is that this is going to stop the development of LDTs – maybe not all, but many. Or they may be available at a reference lab that’s many miles away with a turnaround time that’s dramatically prolonged. Prolonged turnaround time can mean the difference between the patient getting a vitally important drug at the right moment or getting it too late.”
Waiting for the Trump Administration’s next move
Despite the nature of the Executive Order on deregulation, there is also evidence that suggests the new administration will not be inclined to interfere with the FDA’s final ruling despite it being announced during the previous administration’s term. On 19 FEB 2025, the Department of Justice (DOJ) counsel defended the rule during oral arguments made by lobby groups that represent clinical laboratories before the U.S. District Court for the Eastern District of Texas in Plano. “The attorney representing FDA on Feb. 19 presented the argument against the plaintiffs,” said Karcher. “You could say that at that point the FDA, under the new administration, was continuing to support the final rule. Will they continue to – we don’t know.”
Last March (2024), Karcher testified in front of the U.S. House Committee on Energy and Commerce Subcommittee on Health, stating that the then-proposed rule was unacceptable and that the CAP believed a better framework for the oversight of LDTs was needed. The CAP has also given its support to lawsuits that have been filed against FDA by the American Clinical Laboratory Association and the Association for Molecular Pathology. “We’ve filed an amicus brief in support of both suits,” said Karcher, who is still awaiting a response to the CAP letter written under his signature. “We are requesting that the Trump administration not defend the rule,” he said. “We feel that they should vacate the rule. But we have not yet received an answer or seen any action.”
The proximity of the looming 06 MAY 2025 launch date and the appointment of Martin A. Makary, MD, MPH, as FDA’s New Commissioner could bring more clarity. Of particular importance, says Karcher, is to receive any potential news prior to that first compliance deadline. “We think that’s very important,” he said. “We feel that laboratories should not be forced to begin taking the steps that are necessary to comply with this rule. At this point in time, we’re asking for a ruling quickly.”
Karcher and the CAP continue to stress the importance of compliance; however, and are supporting the industry on the path to compliance through advocacy and education. “While we do not support this rule, we’re providing the information for laboratories to comply with it should they be required to,” Karcher said. “We are presenting a six-part webinar series on how laboratories can comply with the rule. If this ruling stands, we feel strongly that laboratories need to comply. We are absolutely encouraging laboratories to be prepared for compliance should that be necessary. And labs are already beginning to make preparations for that. In the end, what we want is a proper framework that maximally protects patients; but, also allows patients access to these lifesaving tests.”
REFERENCE: Medical Device and Diagnostic Industry (MD+DI); 24 MAR 2025; Moe Darrah)