HHS officials on Monday announced they have formally instructed the Food and Drug Administration to review voluntary Emergency Use Authorization submissions of lab-developed COVID tests.
The instructions reverse a previous FDA decision to no longer review EUA submissions for SARS-CoV-2 LDTS, but a number of questions remain about how broadly they will be applied and how exactly they will be implemented.
On a media call Monday, Brett Giroir, HHS Assistant Secretary said the agency was responding to concerns from university labs that if they were not able to receive EUA for SARS-CoV-2 LDTs they would not have liability protection under the Public Readiness and Emergency Preparedness (PREP) Act. The PREP Act gives test providers immunity from liability claims stemming from the use of tests (or other disease countermeasures) during a public health emergency, but it provides this protection only for tests that have EUA.
He specifically cited a conversation with Sen. Amy Klobuchar (D-Minn.) about the University of Minnesota's concerns around PREP liability protection and COVID testing.
Giroir said that he had instructed the FDA to review EUA applications in a timely manner, and if the agency was not able to complete the reviews within 14 days it was to send the submission to the National Cancer Institute for review.
The move by Giroir is the latest in an ongoing conflict between HHS and the FDA over the latter's authority to regulate LDTs.
In August, HHS announced that it had determined that the FDA would not require premarket review of LDTs without notice-and-comment rulemaking, seemingly resolving the role of the agency in LDT regulation, an issue that has hung over the lab business for almost three decades.
The HHS move appeared to be inspired by the pandemic, with the department noting that its recission of FDA guidances and other informal issuances concerning premarket review of LDTs was "part of HHS's ongoing department-wide review of regulatory flexibilities enacted since the start of COVID-19."
The decision removed the requirement that CLIA labs take COVID lab developed tests through the FDA's emergency use authorization process. However, even with that requirement removed, there was still incentive for labs to submit LDTs for EUA. EUA status is perceived by many healthcare providers as a signal of test quality, and so a test with EUA could have a competitive advantage from a sales perspective.
There was also a reimbursement angle. Under the Family First Coronavirus Act (FFCRA), most commercial payors must cover medically necessary COVID testing without cost sharing, prior authorization or other medical management requirements, and the legislation requires payors to cover testing by out-of-network labs. These requirements only cover tests with EUA, however, giving labs reason to continue taking their COVID LDTs through the EUA process.
Additionally, there was the fact that PREP liability protection covered only tests with EUA.
These concerns came to the fore in October when the FDA announced that it would no longer review SARS-CoV-2 LDTs for EUA, essentially shutting new LDTs out from the benefits offered by EUA status.
The agency framed the decision as a move to focus its limited resources towards reviewing EUA requests for tests like point-of-care and home-based assays that could allow for higher-throughput and more widely distributed SARS-CoV-2 testing. Timothy Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA's Center for Devices and Radiological Health, added that HHS's determination that the FDA could not require premarket review of laboratory-developed tests without notice and comment rulemaking influenced the agency's decision to stop reviewing LDTs for EUA.
During a webinar hosted last month by 360Dx, Elizabeth Hillebrenner, associate director for scientific and regulatory programs at CDRH, expanded on Stenzel's comments.
"The HHS statement indicates that FDA authority can only be exercised for these tests following a lengthy notice and comment rulemaking process, which is not feasible to address the current public health need," she said. She added that this notice and comment rulemaking requirement meant the agency "may not be able to remove a poorly performing LDT from the market or take other necessary steps to assure that these tests for COVID-19 are accurate, safe, and reliable. So we need to focus our efforts where we can do that."
Giroir's instructions this week would seem to reverse the agency's decision, but a number of questions regarding how they will be implemented remain unanswered, said Jeff Gibbs, a director at the law firm Hyman, Phelps & McNamara, who formerly served as the FDA's associate general counsel for enforcement.
First, he noted, it is unclear to which labs the policy laid out by Giroir will apply. Giroir said that the move was aimed primarily at providing PREP liability protection to universities but added that it would apply to health systems developing LDTs, as well. He did not specify what other kinds of labs it might apply to or if it covered any facility offering SARS-CoV-2 LDTs.
HHS did not respond to requests for comment as of press time.
In a statement, Julie Khani, President of the American Clinical Laboratory Association, which represents many large commercial lab companies, applauded the decision.
"Many of the tests that have been granted EUAs for COVID-19 testing are innovative, high-throughput LDTs that have reduced reliance on supplies and been integral to expanding testing capacity," she said. "These are exactly the kinds of tests that FDA has stated it wants to prioritize. ACLA believes the FDA should continue to allow labs to voluntarily submit EUAs for FDA review and authorization."
Gibbs said that questions also remained regarding the basic mechanics of the process. For instance, will EUA submissions be sent to NCI for review after they have gone unreviewed at the FDA for 14 days or will they go to NCI straight away if FDA has a 14-day backlog? How long will NCI have to review EUA submissions and to what standard and by what criteria will it review them?
He added that it was an unusual role for NCI given that the institute is not a regulatory body. NCI has helped validate SARS-CoV-2 serology tests during the pandemic, using expertise within its human papillomavirus (HPV) serology testing lab. That effort, however, consisted of more traditional validation work, as opposed to the regulatory role NCI is apparently now being asked to play.
Meanwhile, the FDA appeared to push back on Giroir's comments, maintaining in a Monday update of its SARS-CoV-2 testing FAQ page that it was "declining to review EUA requests for LDTs at this time."
An agency spokesperson declined to comment on whether this reflected its current policy on reviewing EUA submissions for LDTs and referred 360Dx to HHS.
This story first appeared in our sister publication, 360Dx, which provides in-depth coverage of in vitro diagnostics and the clinical lab market.