For SARS-CoV-2, clearing the air on EUA tests

Charna Albert

July 2023—As the COVID-19 federal public health emergency drew to a close in mid-May, industry experts explained what will and won’t change for the laboratory and weighed the fallout from the drop-off in SARS-CoV-2 testing.

Alesia McKeown, PhD, scientific partner at Roche Diagnostics, in mid-May addressed customer concerns that with the end of the public health emergency laboratories would be required to use only FDA-cleared SARS-CoV-2 tests or use the EUA product as a high-complexity test. “The end of the public health emergency does not impact ability to utilize EUA tests for continued diagnosis of SARS-CoV-2, regardless of complexity or CLIA categorization,” Dr. McKeown says.

The Food and Drug Administration hasn’t yet set a date for the end of the SARS-CoV-2 emergency use authorization, Adam Borden, senior vice president of policy and strategy at the American Clinical Laboratory Association, said in a May webinar hosted by Roche. The FDA will give at least 180 days’ notice before the termination date, after which manufacturers will be permitted to continue distributing EUA test kits if the company sends a premarket submission to the FDA before the termination date. Laboratories will be allowed to use their stock of EUA test kits through the tests’ expiration date even if the manufacturer hasn’t sent a premarket submission to the FDA, he said. For now, the agency will continue to issue new EUAs, and laboratories can continue to order EUA test kits.

The FDA has not said it will publish where manufacturers are in the regulatory process, Borden said. “It’s best to make sure you connect with your manufacturers to know where they are—if they’ve submitted already, what their timeframe is.”

“But again, we don’t have that EUA termination date yet,” he added.

Roche is communicating closely with the FDA to support the transition for IVD clearance of its EUA products, Dr. McKeown says. “We are working to ensure that patients and our customers have access to the testing solutions they need to provide accurate diagnosis across the continuum of care, now and in the post-pandemic era.”

For laboratory-developed SARS-CoV-2 tests, following the EUA termination date the FDA will revert to its normal enforcement discretion policy for LDTs. This will include LDTs that have EUAs and new SARS-CoV-2 tests developed in the future.

Daniel Rhoads, MD, assistant professor and section head of microbiology at the Cleveland Clinic and vice chair of the CAP Microbiology Committee, thinks the FDA might allow some SARS-CoV-2 EUA testing to continue into the future. “I wouldn’t be surprised if the FDA says, ‘There are a lot of options on the market and many manufacturers have moved to 510(k)—there’s no reason to maintain EUA because there are good solutions to meet the needs of the public that already have achieved full regulatory clearance.’ But I also wouldn’t be surprised if they said, ‘There’s a little bit of EUA still on the market, but it’s not causing any harm; the risk is low. We’re not going to push everybody to discontinue EUA testing.’” Diagnostic tests for the Ebola and Zika viruses and several others still are under EUA.

Dr. Rhoads expects the transition to IVD to be relatively simple for the laboratory. “If the chemistry and assay stay the same, and manufacturers are just getting a different regulatory mark, that should be straightforward. However, if there’s a need to optimize assay chemistry or remove an EUA indication like asymptomatic screening at the same or a similar time as changing the regulatory labeling, that will potentially cause confusion and be more challenging,” he says. “Specifically, laboratories will need to determine what changes, if any, accompany the updated regulatory labeling. If it is a fundamentally different assay, then it needs to be validated in vitro anew.”

“I don’t expect a lot of this to happen, but it might happen,” he continues. Cepheid is an example of a company that has updated its chemistry. “So there is precedent that manufacturers optimize their chemistry to keep up with the mutations and the viruses.” Other manufacturers, he says, have begun to receive FDA clearance for combination assays that never had EUA, such as the Hologic Panther Fusion SARS-CoV-2/Flu A/B/RSV assay. “Although the pace of change has slowed, we haven’t yet achieved a steady state,” Dr. Rhoads says. “Transitioning away from EUA and toward FDA-cleared devices will be a step toward a steadier state.”

As more manufacturers seek 510(k) clearance, they could see a slowdown at the FDA, says Larry Worden, founder and principal of IVD Logix, a market research and consulting firm. It won’t recall the early days of the pandemic, when the FDA was unable to accommodate any pending submissions other than EUA review, “but it’s going to be a challenge and everybody can expect longer regulatory approval processes.”

Companies that entered the market during the pandemic may put in a premarket submission for their EUA products but fail to make it through the full regulatory process. “If you have a submission in process, your EUA will not end. It’s an incentive to put something in, to extend your available marketing time,” Worden explains. Though the products may be well suited to a regulatory submission—“these tests were used at high volumes and gained a large experience base and potentially clinical data”—many of these companies lack the experience needed to navigate the regulatory process, he says. The difficulty isn’t in putting in the marketing submission; rather, “it’s doing it practically and doing it with the forethought of what’s going to be needed to see it through to the end.”

Some of the non-clinical companies that expanded into SARS-CoV-2 testing because of the immediate need, such as those in environmental testing or research tools markets, hoped to use pandemic revenue to broaden their offerings and compete in the clinical molecular PCR market. “A lot of the companies that received [SARS-CoV-2] emergency use authorizations were naive in terms of regulation and reimbursement,” Worden says. “They entered the market when the hurdles were low.” IVD Logix worked with a number of these companies to outline “the shape and size of the clinical market,” the test development challenges and other hurdles, and the expertise of the established companies, he says. “Some of them decided to give it a shot anyway and introduced themselves as broader line in vitro diagnostic companies, and they have not succeeded.”

Of the structure of the IVD industry post-pandemic, Worden says it’s the established in vitro diagnostic companies that ultimately are going to benefit. “We began to see consolidation even before the end of the pandemic, when a lot of the testing went back to the large manufacturers once they had the ability to meet demand.” The top 10 IVD companies typically represent about 65 to 70 percent of total global revenue, he says. “In molecular, if you look at just that segment, the top 10 represent about 90 percent, as a result of COVID.”

With the end of the public health emergency, Medicare reimbursement for high-throughput molecular SARS-CoV-2 testing reverted from an enhanced rate of $75 plus $25 for results within two days to the standard rate of $51. ACLA’s Borden said in the Roche webinar that private payers will not necessarily be held to that price. The enhanced rate was for high-throughput standalone SARS-CoV-2 testing only; Medicare rates for multiplex testing have not changed, Borden tells CAP TODAY. “They could change from the private payer side, but that’s all negotiations between the provider and the payer.”

The enhanced rate for high-throughput testing, which early in the pandemic was set at a flat rate of $100, was critical to developing laboratory capacity and supporting the buildout of infrastructure, he says. “It was helpful on the innovation side, but also for growing capacity.” Borden expects testing capacity to remain strong among ACLA members, though some smaller laboratories may curtail SARS-CoV-2 testing. “We would have preferred to have the enhanced rate, to ensure that capacity.”

When the emergency was in effect laboratories were required to publish their SARS-CoV-2 testing prices, and payers were required to pay the published price if no other rate was negotiated. With the end of that policy, Borden says, some payers are communicating new payment rates for tests. “That’s something that is coming out of the end of the public health emergency.”

One policy that has not changed with the end of the emergency: The Centers for Medicare and Medicaid Services is allowing remote review of digital laboratory data to continue, without the remote testing site having to obtain a separate CLIA certificate. Remote review of physical slides is no longer permitted.

Initially, Borden says, the CMS indicated that only pathologists would be permitted to continue remote review of digital materials after the emergency’s end. On May 11 the agency extended its enforcement discretion for remote review to other laboratory personnel. “It’s welcome news,” he says. “And ACLA did advocate on that topic throughout the year.”

Lisa-Jean Clifford, chief operating officer and chief strategy officer, Gestalt Diagnostics, calls the decision to continue allowing remote review “a turning point” for the digital diagnostics industry and says the regulatory bodies are “coming up to speed” in understanding the logistical differences between remote review of digital images and remote review of physical slides.