HHS Reinstates FDA Premarket Review of LDTs

On again, off again, and now on again. In a surprising reversal, the US Food and Drug Administration (FDA) announced that it’s taking back its policy of not enforcing premarket review requirements for Laboratory Developed Tests (LDTs). The Nov. 15 announcement is the second 180⁰ turn in LDTs premarket approval policy in just over a year. Here’s a briefing on the new policy and its likely impact on new lab tests in both the near and long term.

How FDA Regulates LDTs

Confusion, contradiction and inconsistency have been the hallmark of FDA LDTs regulation from the very beginning. Because the original legislation that established the FDA and its current regulatory system didn’t address lab tests, the agency has had to shoehorn its powers over medical devices to regulate LDTs. Specifically, it required LDTs to obtain premarket approval through the 510(k) pathway it uses to clear new devices. In addition to challenging the FDA’s authority over LDTs, the lab industry has long objected to the agency’s practice of skirting the regulatory process and relying on guidance, website statements and other informal issuances to make regulatory policy. 

LDTs Regulation during the COVID-19 Crisis

The COVID-19 public health emergency exposed the weaknesses in the FDA’s makeshift system. The agency’s initial attempts to assert premarket control over LDTs at a time when innovative COVID-19 tests were in desperate need drew widespread criticism. FDA red tape was seen as hampering the effectiveness of pandemic response.

The FDA responded in March 2020 by unveiling a new policy that empowers labs to develop and utilize their own tests, provided that they notify the agency that they were shipping products. In May, when it had become clear that the new policy had gone too far in the other direction by allowing for junk tests to reach the market, the FDA changed course by requiring Emergency Use Authorization (EUA) for diagnostic tests.

The next twist came in August 2020 when HHS took matters into its own hand by ordering FDA not to require premarket review for LDTs. The move, which was part of the Trump administration’s broader efforts to cut red tape impeding business, caught the lab industry by surprise and drew widespread criticism, including from influential former FDA Commissioner Scott Gottlieb, who warned of the new policy’s potential to undermine the agency’s ability to provide critical advice to test developers and crack down on bad tests.

New Policy Restores Premarket Review of LDTs

The LDTs regulatory policy pendulum has now swung back again. Supplies of COVID-19 tests have stabilized. And the agency has had to recall a number of new tests amid concerns about their accuracy. On Nov. 15, HHS announced that the previous policy of allowing makers of LDTs to bypass the 510(k) premarket review clearance and EUA processes has impaired FDA’s ability to address problematic COVID-19 tests. From now on, according to HHS Xavier Becerra, the historical review rules will apply and LDTs won’t receive separate treatment.

Consequences: Test makers currently offering tests launched without submission of an EUA request will have to submit an EUA request. In addition, the agency will review pending EUA request submissions for LDTs. If the agency doesn’t subsequently approve the EUA request, it will notify the test maker who will then have to stop marketing the product within 15 calendar days.

The New HHS Policy on EUAs

The new policy also establishes new limits on which tests can get EUA, reserving the EUA process for:

• At-home and point of care (POC) tests for use on a prescription and over-the-counter (OTC) basis that can be manufactured in large volumes;
• Tests that expand testing capacity such as through specimen pooling;
• High-volume, lab-based molecular diagnostic tests in which specimens are collected at home and shipped to a lab;
• Tests for screening asymptomatic people;
• Tests detecting multiple different types of respiratory viruses at once;
• Lab-based and POC high-volume antibody tests measuring the amount of antibodies, such as fully quantitative antibody tests that measure neutralizing antibodies; and
• Tests for which the request is from a US government entity, such as the Biomedical Advanced Research and Development Authority (BARDA) or the US National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) initiative.

Developers of tests not on the EUA reserve list will have to rely on 510(k) clearance, de novo classification and other traditional regulatory pathways.

The Long-Term Outlook for LDTs Regulation

The COVID-19 public health emergency has given makers of LDTs more than 18 months of unprecedented relief from FDA regulation. Through November 2021, FDA has authorized over 420 tests and sample collection devices for COVID-19, the agency notes. Recent authorizations alone could result in up to 400 million OTC tests available monthly in the US by early 2022. Globally, COVID-19 testing has grown to become a $31.5 billion market, according to Kalorama Information.

However, we’ve now come to a new stage, one that Winston Churchill might have described as representing not the beginning of the end but the end of the beginning. With COVID-19 tests now in ample supply, FDA no longer needs to relax its standards and can resume its historical scrutiny over new LDTs. So, even though it represents a massive reversal of Trump era policies, the new Biden administration policy should stabilize the LDTs regulation situation for a while.

However, the long-term effort and need to establish a legitimate, legislative-rooted regulatory system for regulation of LDTs will remain, whether via creation of a risk-based framework specific to diagnostics that includes a new test product category for LDTs, as proposed by the Verifying Accurate, Leading-edge IVCT Development (VALID) Act, transferring the FDA’s regulatory authority over LDTs to HHS, as proposed by Verified Innovative Testing in American Laboratories (VITAL) Act or some other approach.