FDA Imposes New Limits on COVID-19 Tests with Access to EUA Pathway

On Nov. 15, the US Department of Health and Human Services (HHS) stunned the laboratory industry by announcing that the US Food and Drug Administration (FDA) would once more require new COVID-19 Laboratory Developed Tests (LDTs) to go through premarket review. And as if losing the temporary reprieve afforded by the August 2020 policy removing LDCs from the ambit of premarket regulation that applies to novel medical devices, HHS inflicted another blow on test makers by narrowing who will have access to the FDA Emergency Use Authorization (EUA) pathway for new SARS-CoV-2 diagnostic tests. Here is a quick briefing.

EUA Clearance of SARS-CoV-2 Tests

Hundreds of new COVID-19 diagnostic tests have reached the US market through the EUA pathway since the public health emergency began in February 2020. Through November 2021, FDA has authorized over 420 tests and sample collection devices for COVID-19, according to the agency. Recent authorizations alone could result in up to 400 million over-the-counter (OTC) tests being available monthly in the US by early 2022.

However, the agency clearly has mixed feelings about this unprecedented binge in EUA clearances. The FDA notes that “many of the COVID-19 tests offered prior to FDA review were determined to have poor performance.” Obvious examples are the current Class I recalls of at-home rapid point-of-care (POC) tests from Ellume and Abbott Laboratories amid concerns over accuracy and the risks of reporting false positive results. And as supplies of new COVID-19 tests stabilize, the agency feels the time has come to pull back on prior leniency and reassert regulatory authority.

Which SARS-CoV-2 Tests Will Have Access to EUA Pathway

The Nov. 15 HHS policy establishes new limits on which tests for SARS-CoV-2 will be able to get EUA. Specifically, FDA will concentrate on high throughput tests that can be manufactured in large volumes, including at-home and POC tests for use on a prescription and OTC basis. Also receiving priority will be SARS-CoV-2 assays and diagnostics that offer the potential to expand testing capacity, including:

• Tests that can be performed on using specimen pooling methods;
• High-volume, laboratory-based molecular diagnostic tests in which specimens are collected at home and shipped to a laboratory;
• Tests designed for screening asymptomatic populations; and
• Multianalyte and other tests that are capable of detecting multiple different types of respiratory viruses at once.

Access to the EUA pathway will also remain open to laboratory-based and POC high-volume antibody tests that measure the amount of antibodies in a patient’s system, such as fully quantitative antibody tests that measure neutralizing antibodies.

Finally, FDA will also afford priority to tests for which request for EUA clearance comes 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.

Impact on Laboratories

As a result of the new policy, developers of LDTs for SARS-CoV-2 that are not on the EUA reserve list will have to rely on 510(k) clearance, de novo classification and other traditional regulatory pathways to reach the market. Meanwhile, test makers that submitted an EUA request before the new policy was issued can continue to offer the test while the FDA reviews the EUA request, as long as they either:

• Submitted the request after Feb. 1, 2021; or
• Confirm to the FDA within the next 45 days that they want the agency to continue reviewing their request.

The new HHS policy and recent pattern of flip flopping on FDA regulation of LDTs drew criticism from the leading trade association for laboratories and developers of new laboratory tests, the American Clinical Laboratory Association (ACLA). “While we appreciate the administration’s focus on the need for high-quality testing, continually shifting regulatory policies creates uncertainty and undermines patient access to lifesaving diagnostics,” noted the ACLA statement.

Takeaway: The Need for LDTs Regulatory Reform

The ACLA statement is best understood as a venting of long pent-up frustrations over the way FDA regulates LDTs. The ACLA hits the nail right on the head in pointing out that this most recent reversal of regulatory policy only serves to underscore what the laboratory industry, law makers and regulators themselves have known all too well for over a decade: LDTs regulation on the fly does not work. Or, in the ACLA’s words, there is a “clear need for comprehensive diagnostic reform legislation that can provide long-term clarity and continuity for clinical labs and their work to support medical breakthroughs moving forward.”

While FDA has sought to control the process, it appears increasingly likely that LDTs reform, to the extent it is ever achieved, will come through the legislative rather than the regulatory process. Currently, there are two competing models working their way through Congress, including:

• VALID, i.e., the Verifying Accurate, Leading-edge IVCT Development Act, which would leave FDA in control of LDTs but replace the current improvisational-based rules with a formal, legitimate risk-based framework in which LDTs would no longer be treated as an offshoot of new medical devices regulation but instead be in their own separate test product category; and
• VITAL, i.e., the Verified Innovative Testing in American Laboratories (VITAL) Act, which would shift LDTs regulation away from FDA and to HHS as an extension of its regulatory authority over laboratory operations and products under the Clinical Laboratory Improvements Act (CLIA).

Either option—or even a third approach—would almost certainly constitute an improvement over the current chaos, confusion and inconsistency created when agencies unbound by statutory limitations or the constraints of formal federal rule making are free to just make up the rules as they go along.