Like a prizefighter who’s determined to win despite umpteen blows to the face, the FDA is ready for the next round in its years-long effort to regulate laboratory-developed tests (LDTs) — in vitro diagnostic (IVD) tests that are designed, manufactured and used within a single laboratory.

In the Biden administration’s latest Unified Agenda (more formerly, the Unified Agenda of Regulatory and Deregulatory Actions — a semiannual list of the actions that federal agencies plan to take during the upcoming months), the agency announced its intention to amend its regulations “to make explicit that [LDTs] are devices under the Federal Food, Drug, and Cosmetic Act” — making them subject to the FDA’s full regulatory oversight.

Released June 13, the Unified Agenda indicated that a new FDA proposed rule for LDTs may be published as soon as August.

Claiming the Authority

For years, the FDA has argued that under the statute it has comprehensive regulatory authority over all IVD tests, including LDTs, as part of its authority to regulate medical devices.

Nevertheless, the agency had not enforced the authority over LDTs that it claimed because typically the tests had been “relatively simple” and available only on a limited basis.

Eventually, however, the FDA grew concerned that LDTs were becoming riskier and more complex. Some LDTs that had never come under the agency’s scrutiny were being used to detect serious diseases like breast cancer and Alzheimer’s. Also, use of some of the tests had exploded to the point that they could have a nationwide reach.

In July 2014, the FDA released a draft “framework for regulatory oversight” of LDTs. In the draft framework, the agency signaled its intention to ramp up enforcement of regulatory requirements for the tests.

The agency said at the time that it was proposing “a risk-based, phased-in framework for oversight of LDTs in a manner that is consistent with FDA’s current regulation of [IVD] devices.”

Under the framework, regulatory requirements would have been phased in over particular periods of time for various types of LDTs, depending on their level of risk.

In support of the proposed framework, in November 2015 the FDA published a report presenting 20 case studies of LDTs that had produced false or inaccurate results. Such tests, the agency said, could cause patients to “undergo unnecessary treatments and potentially delay diagnosis of their true condition.”

Pushback

There was substantial opposition to the proposed framework from some stakeholders, including calls for the FDA to withdraw the framework and any guidance released in connection with the framework. The stakeholders insisted that any changes in the regulatory treatment of LDTs could be established only through a full agency rulemaking procedure.

In November 2016, the FDA announced that it was postponing the release of any final guidance on the agency’s regulation of LDTs, saying that it would work with the incoming Trump administration and Congress to devise a comprehensive regulatory approach.

A week before President Trump took office, the agency posted a discussion paper that it said was intended to “simply advance the public discussion” by providing a possible approach.

In August 2020, the Department of Health and Human Services (HHS) announced a policy aimed at restricting the FDA’s regulation of LDTs. Under the policy, the FDA could not require premarket review of LDTs “absent notice-and-comment rulemaking, as opposed to through guidance documents, compliance manuals, website statements or other informal issuances.”

The Swing Back Toward Regulation

In September 2021, a few months after it took office, the Biden administration withdrew the Trump administration policy, with HHS saying that it no longer had a policy on LDTs that was separate from the FDA’s “longstanding approach” toward the tests.

On the same day, the FDA toughened its requirements for all new COVID-19 diagnostic tests, including LDTs, announcing that it expected any new COVID test to have an emergency use authorization (EUA) or a traditional device premarket authorization such as a de novo classification or a cleared 510(k).

Congress Steps In

As the FDA again inched toward more regulatory oversight of LDTs, some in Congress supported legislation to block the agency from regulating the tests, even during a public health emergency.

Meanwhile, multiple versions of the proposed Verifying Accurate Leading-edge IVCT Development Act (VALID Act), which would address LDTs as part of a broad reform to how the FDA regulates in vitro clinical tests (IVCTs), were introduced in Congress.

Last year, VALID Act provisions made it into a device user fee bill that passed a Senate committee, but the provisions weren’t included in either the final user fee legislation (the Medical Device User Fee Amendments of 2022, MDUFA V) or the set of FDA reforms enacted separately at the end of 2022 (the Food and Drug Omnibus Reform Act of 2022, FDORA) — despite the efforts of the device industry, which called for an end to the ongoing regulatory uncertainty.

New Calls for Regulation

Just before the Unified Agenda notice was released, 16 public interest groups urged the FDA to act to regulate LDTs if Congress does not act.

Also, on May 11, FDA Commissioner Dr. Robert M. Califf told a House committee that the agency would act to make LDTs less risky, saying, “We intend to move forward using our current regulatory authorities to offer providers and patients confidence in the diagnostic tests that they use.”

The FDA again signaled its concerns about LDTs when it announced a pilot program for cancer drugs on June 10. Under the program, the agency will ask oncology drug manufacturers to submit information about the IVD tests they used to enroll patients in clinical trials involving their products. After evaluating the information submitted, the FDA plans to post online recommended minimal performance characteristics for the tests.

Stay Tuned

Whenever the FDA’s proposed rule on LDTs appears, and to whatever extent the agency proposes to oversee the tests, the agency’s action is certain to signal another round of the marathon regulatory boxing match over the tests, potentially including challenges in the courts — with resistance coming from labs, members of Congress, trade associations and other stakeholders.

Whatever happens, all indications are that the FDA is set to jump back into the ring, ready to go the distance toward establishing a comprehensive set of regulatory requirements for LDTs.