Lab worker looks at test tube

The Department of Health and Human Service’s (HHS) recent announcement that the Food and Drug Administration (FDA) will not require premarket review of laboratory developed tests (LDTs) absent notice-and-comment rulemaking has raised new questions about future oversight of LDTs.

At the beginning of the COVID-19 pandemic, FDA first required laboratories to obtain emergency use authorization (EUA) before using LDTs to detect SARS-CoV-2. After pushback from AACC and other laboratory groups, FDA announced a policy under which clinical laboratories still need an EUA, but they could begin using LDTs immediately pending FDA review. While FDA typically has not required such premarket review for LDTs, the agency has maintained that it has the authority to require such review.

This change, detailed in an August 19 notice, first indicated that clinical laboratories may still voluntarily seek EUA for LDTs, but they are not required to do so. On October 7, FDA posted another update that it would no longer review EUA requests for LDTs. “FDA continues to prioritize review of EUA requests for POC tests, home collection tests, at-home tests, tests that reduce reliance on test supplies, and high-throughput, widely distributed tests,” the agency posted on its website.

Laboratories that offer such LDTs without premarket authorization will not be eligible for liability protection under the Public Readiness and Emergency Preparedness Act. Clinical laboratories that have already obtained an EUA or other marketing authorization for an LDT are not affected by the announcement.

While the notice referenced LDTs to test for SARS-CoV-2, the implications of this change are much broader, affecting all LDTs. In a frequently asked questions (FAQs) document posted shortly after the announcement, HHS said the notice is broadly applicable to all LDTs, regardless of what they are testing for.

“The decision means FDA will have to take a step back and go through the appropriate channels in order to regulate LDTs,” said Patricia Jones, PhD, DABCC, FADLM, clinical director of the chemistry and metabolic disease lab at Children’s Medical Center of Dallas and chair of AACC’s Policy and External Affairs Committee. “The notice doesn’t say FDA can’t regulate LDTs; it just says the agency can’t do it without formal rulemaking. It gives labs a bit of a breather.”

FDA’s jurisdiction to regulate LDTs under the medical device provisions of the Federal Food, Drug, and Cosmetic Act has long been the subject of debate. FDA for years has asserted that it has legal authority over LDTs but has chosen to exercise “enforcement discretion” not to regulate such tests in most situations. The clinical laboratory community disagrees and maintains that tests developed in clinical labs for use only in those labs should not be subject to FDA oversight.

FDA several times has tried to define just what its role should be in overseeing LDTs. In October 2014, the agency issued a controversial draft guidance proposing a framework for regulatory oversight of LDTs, including, among other things, phasing in premarket review of most LDTs. In November 2016, FDA then said it would not finalize this guidance document. But in January 2017, the agency issued a “discussion paper” regarding another proposed framework for LDTs that included, among other things, premarket review.

Congress has also tried to tackle the thorny issue of LDT oversight, though efforts in the past have failed. Sen. Rand Paul (R-Ky.) tried again this year, introducing the Verified Innovative Testing in American Laboratories (VITAL) Act, which would accelerate test approval during public health emergencies by codifying that current federal regulations place oversight of LDTs under CLIA. AACC, which endorsed the VITAL Act, has long held that LDTs are already regulated under CLIA and do not need an additional layer of oversight from FDA. The VITAL Act was referred to committee, but no action has yet been taken on it.

Another measure, the Verifying Accurate and Leading-Edge IVCT Development (VALID) Act, also was introduced this year. This legislation attempts to set out a regulatory framework for in vitro clinical tests (IVCTs), which would cover an array of clinical tests, including LDTs and in vitro diagnostics (IVDs) sold to laboratories by manufacturers. AACC opposes the VALID Act, arguing that giving FDA new, expansive powers to regulate LDTs would result in decreased patient access to essential medical tests.

Notice Only Applies to Premarket Review

HHS’s announcement does not question FDA’s long-standing position that it has the statutory authority to regulate LDTs as medical devices and that its LDT policies have been grounded in enforcement discretion, notes Greg Levine, an attorney with Ropes & Gray in Washington, D.C. Nor does the announcement deal with any aspect of FDA regulatory oversight other than “premarket review.”

The HHS FAQs specifically state, “Although FDA has asserted the authority to do so, [the premarket review] requirement has in fact almost never been enforced. It was only being enforced during public health emergencies, and we are simply reverting to the same level of regulatory requirements that were in place during all other times.”

The announcement does, however, acknowledge that FDA could, at least theoretically, seek to impose premarket review requirements for LDTs through notice and comment rulemaking, though Levine noted that FDA’s efforts to assert its regulatory authority over LDTs have stalled in recent years, and FDA appears to have resigned itself to waiting for congressional action.

“It is possible HHS’s announcement could spur Congress to take such action,” Levine said. “However, in an election year, the passage of LDT legislation by the current Congress, such as the VALID Act, remains unlikely.”

HHS Faces Criticism

While the laboratory community has largely praised HHS’s August 19 notice, Scott Gottlieb, FDA commissioner from 2017 to 2019, has criticized the decision, saying that it could hinder FDA’s ability to protect public health. In a series of tweets shortly after the notice was announced, Gottlieb argued the HHS decision will have potentially dire consequences for the nation’s response to COVID-19.

“For the last 6 months, FDA’s device center worked effectively with labs to advance hundreds of tests for COVID,” he wrote. “A new policy that extricates FDA from this work—and goes further, by removing any FDA role over any lab developed test—could put this work at risk.”

Gottlieb also said the decision means FDA might not be able to provide critical advice to test developers or take needed enforcement actions against bad tests. “We’ll see a plethora of [direct-to-consumer] COVID tests enter the market, where tests ship directly to consumers and are processed in a central lab operating outside FDA oversight,” he tweeted.

Levine, however, emphasized that the notice does not take away FDA’s ability to crack down on test developers who make false claims. While FDA will not be able to pursue enforcement for failure to comply with premarket review requirements, false and misleading labeling and promotion claims will continue to be fair game for FDA, the Federal Trade Commission, Department of Justice, and state regulators under applicable consumer protection and fraud statutes, he said.

However, Jeff Gibbs, an attorney with Hyman, Phelps & McNamara and contributor to the FDA Law Blog, believes there is some ambiguity on this point, noting that FDA’s previous actions against labs whose tests were considered unsafe or misbranded were based on the agency’s position that it has the authority to regulate LDTs.

“HHS’s announcement, while short on specifics, apparently takes the position that FDA can’t regulate LDTs absent rulemaking,” he said. “Given that, it is difficult to see the legal basis that FDA could assert to support action against a lab, even if FDA deemed a test to be unsafe or the lab’s claims to be false. FDA has no general mandate to regulate laboratory developed tests.”

Developing a Common Regulatory Framework

Two senior managers at FDA also pushed back against the decision not to require premarket review for SARS-CoV-2 LDTs. In an editorial published September 9 in the New England Journal of Medicine, Jeff Shuren, MD, JD, and Timothy Stenzel, MD, PhD, wrote that they believe FDA has a role in overseeing clinical tests, whether they are developed by commercial manufacturers or by laboratories, especially during a public health emergency. Shuren is director of FDA’s Center for Devices and Radiological Health, and Stenzel is director of the Office of In Vitro Diagnostics and Radiological Health.

Whether developed by an IVD company or a clinical laboratory, diagnostic tests should undergo thorough review, according to Shuren and Stenzel. “We need common approaches to validating test design and performance, regardless of whether there is an emergency,” they wrote. “Our experience with COVID-19 highlights the need for a common legislative framework to ensure that all clinical tests are accurate and reliable.”

Jones agrees that a regulatory framework is necessary, but she believes the basic framework already exists in CLIA. “CLIA does need to be updated, but I don’t think we need to create a new regulatory structure under FDA. We already have the structure in place.”

Kimberly Scott is a freelance writer who lives in Lewes, Delaware. +Email: [email protected]