The rescission order directing the U.S. FDA to abandon regulation of lab-developed tests is scarcely three weeks in the past, but two senior managers at the FDA are pushing back in an editorial appearing in the New England Journal of Medicine. The FDA’s Jeff Shuren and Tim Stenzel wrote that there is “a need for a common legislative framework” to ensure clinical tests are accurate and reliable, which implicitly concedes that the statute does not authorize the agency to regulate lab-developed tests. However, this passage also flies against the HHS rescission order’s assertion that “duplicative regulations and unnecessary policies” have hampered the response to the COVID-19 pandemic, highlighting an apparent split between HHS policymakers and FDA staff.

At the outset, the rescission order seemed to frame the controversy in the context of the pandemic. However, the Department of Health and Human Services made note of Trump administration executive orders that reflect an effort to get federal government agencies out of the way when regulation creates more problems than it solves. Stakeholders offered varying perspectives on the advisability of such a move, although labs that offer tests outside the FDA’s conventional and pandemic-driven regulatory frameworks will not enjoy immunity from litigation for any tests for the SARS-CoV-2 virus.

It might also be pointed out that the rescission order does not take an explicit stand on the point of whether legislation is needed to authorize FDA regulation of lab-developed tests (LDTs), while the reference to duplicative regulations would seem to suggest that HHS believes the FDA does enjoy such statutory authority. However, HHS subsequently posted a FAQ page for the rescission order, which said that the FDA is still empowered to regulate LDTs under the Public Health Service Act. Conversely, the PHS is directed toward federal government response to public health emergencies rather than normal circumstances.

Large production of small number of tests advocated

The Shuren/Stenzel editorial is titled to emphasize “lessons learned” from the pandemic, and said that among the lessons learned is that a public health crisis might be better met by authorization of “a small number of well-designed, well-developed and validated tests” that could be run on commonly installed high-throughput platforms. These would be accompanied by a small number of point-of-care (POC) tests that would be manufactured in large quantities, and Stenzel and Shuren said this approach would be more efficient than the simultaneous development and authorization of “scores of diagnostics.”

However, the duo also asserted a need for “common approaches to validating test design and performance, regardless of whether there is an emergency.” This paragraph goes on to say that the agency’s experience with this pandemic “highlights the need for a common legislative framework to ensure that all clinical tests are accurate and reliable.”

As matters currently stand, the Verifying Accurate, Leading-edge IVCT Development (VALID) Act of 2020 is the primary vehicle for such authorization, although the House version is stuck at two co-sponsors. This is the same standing seen in the Senate version, and neither bill has been heard in committee.

Shuren and Stenzel said that the agency had commenced engagement with clinical labs and commercial test developers in January “to help foster test development.” Initially, the agency provided emergency use authorizations for tests when those tests were validated via “a computer analysis indicating the percentage of identity matches with publicly available SARS-CoV-2 sequences.” The FDA subsequently changed gears to requiring that tests be validated against samples of tissues with known levels of viral load, although validation by means of a standard set of patient samples would have been the agency’s preferred approach.

Shuren and Stenzel point to the Feb. 29 policy for enforcement discretion for labs that had commenced molecular testing upon test validation, a policy that assumes the validation data would be forwarded to the agency within 15 days. However, the authors said this resulted in use of tests with performance problems or the use of poor validation protocols, adding that 82 out of 125 lab EUAs were subject to one or both of these issues.

HPM’s Shapiro says editorial unduly optimistic on FDA regulation

Jeff Shapiro, director of the drug and device practice areas at the D.C. office of Hyman, Phelps & McNamara P.C., told BioWorld that the editorial “suggests that in future pandemics, there should be fewer players in designing and providing tests, even mentioning the CDC as a manufacturer.” Such an approach “may reduce FDA’s workload, but it also risks putting all the eggs in one basket. We should remember that the fiasco with the CDC’s COVID‑19 test at the outset of this pandemic got us off to a very bad start,” he said, adding that a greater degree of centralization of processes “can provide benefits, but it also increases risks, including the risk of failure on a grand scale.”

Shapiro noted that Shuren and Stenzel were “also quite critical of the quality of LDTs developed for COVID‑19, suggesting that FDA oversight has been vital. The jury is still out on that,” Shapiro said.

“In a pandemic when speed was important and resources were scarce, was it wise for FDA to insist on regulating LDTs for COVID‑19? In so doing, FDA created a bottleneck and also limited deployment of their own resources toward other priorities” Shapiro said, adding that the editorial “does not provide a balanced assessment of the costs and benefits of this fateful decision.”

Julie Khani, president of the American Clinical Laboratory Association (ACLA), told BioWorld, “our nation’s experience responding to this pandemic has underscored the essential role played by clinical labs in developing and providing innovative tests to respond to patient and public health needs. The first COVID-19 tests available in the United States, beyond the CDC kits, were highly accurate and reliable LDTs, and ACLA members were among the first to bring these tests to market.”

Khani said also that the pandemic had demonstrated that “a clear and nimble regulatory framework for labs is essential.” She said ACLA “has worked actively with stakeholders for years to advance meaningful comprehensive diagnostic reform,” adding that legislation “is the appropriate vehicle to achieve reform.”

“As we look to the future, it’s critical that any modernized framework encourage innovation and support continued patient access to accurate and reliable laboratory developed tests necessary for the diagnosis, monitoring and treatment of disease,” she said.

The Advanced Medical Technology Association declined to comment for this story. The Association for Molecular Pathology did not respond to contact for comment.

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