New U.S. policies complicate regulatory calculus for COVID-19 antibody tests
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Guidelines released by CMS, HHS and FDA over the past week raise further questions about the flood of antibody tests that have come on the U.S. market without FDA review. At issue is whether the new policies cancel out the benefits of the speedy path to market for serological tests opened by FDA’s March 16 guidance.
At the time the guidelines were released, only one serological test had received Emergency Use Authorization (EUA) from FDA; 94 others had come on the market without review. That balance may shift if regulatory authorization is required for mandatory insurance coverage and permission to run tests at the point of care.
Unlike molecular tests that diagnose COVID-19 by detecting the virus itself, serological tests that detect antibodies against the virus indicate a patient developed an immune response to a past or present infection. These blood tests can be run in high-throughput labs in hours, or via individual dipsticks in minutes at the point of care (see “COVID-19 Diagnostic Tech Tableau”).
As diagnostics, molecular tests require authorization from FDA or state agencies. Serological tests -- positioned as tools to guide decisions such as who can return to work, and where resources should be allocated -- can be marketed without regulatory review, so long as manufacturers perform validation studies, notify FDA and make certain disclaimers.
But the risks posed by inaccurate serological tests are arguably as serious as those posed by faulty diagnostics, particularly if they lead people to resume normal activities while they are still vulnerable to COVID-19.
The challenge of developing tests with enough sensitivity to detect a wide range of COVID-19 antibody responses and enough specificity to ignore antibodies against other coronaviruses -- coupled with reports that serological tests have performed poorly in validation studies -- has cast doubt on hands-off regulatory strategies, and created pressure for governments to ramp up test validation (see “Wild West of COVID-19 Antibody Tests”).
Recent CMS, HHS and FDA policies on insurance coverage, pharmacy access and CLIA lab requirements for COVID-19 tests, respectively, could lead more manufacturers to voluntarily seek review.
The CMS guidance, released April 11, requires private plans to cover COVID-19 diagnostic testing and “certain related items and services provided during a medical visit” with no cost sharing.
Covered tests include those granted EUA by FDA, tests for which developers have requested EUA, and tests authorized by states. The guidance specifies that serological tests will be covered, and points to the sole antibody test with EUA, the qSARS-CoV-2 IgG/IgM Rapid Test from Cellex Inc.
CMS also announced Wednesday it will promote use of high-throughput diagnostic testing by paying nearly double for tests run on more efficient platforms (see “Medicare to Increase High-Throughput COVID-19 testing”).
HHS’s April 8 guidance authorizes retail and independent community-based pharmacies to order and administer COVID-19 tests, including serology tests, that FDA has authorized.
“By doing so, such pharmacists will qualify as ‘covered persons’ under the PREP (Public Readiness and Emergency Preparedness Act) Act. And they may receive immunity under the PREP Act with respect to all claims for loss caused by, arising out of, relating to, or resulting from, the administration or use of FDA-authorized COVID-19 tests,” the department’s Office of the Assistant Secretary for Health (OASH) said in a statement.
Updates to FDA’s website on SARS-CoV-2 testing discussed at an April 8 virtual town hall by the agency’s Center for Devices and Radiologic Health (CDRH) clarify that tests that do not go through EUA are considered “high complexity” by default, which means they can only be performed in high complexity, CLIA-certified laboratories.
The only way for a test to gain “waived” complexity status, and therefore be eligible to be performed in point-of-care settings, such as pharmacies, doctors’ offices and outreach clinics, is to go through EUA. This means rapid serology tests without EUA could only be run as point-of-care tests in high-complexity CLIA labs; otherwise, they must be sent to one, defeating the purpose of their design.
“Certainly it was not our intention to limit the use of these serology rapid serology tests that are otherwise designed to be used in a point-of-care setting. However because of the limits that we have in law it is the opinion of CMS that these can be performed in high complexity labs,” said Timothy Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health, at the meeting.
“If a developer wishes to come through a full EUA authorization process with their point-of-care test that is always a pathway open,” he added.
He said FDA is looking at alternative pathways that could achieve the same end, such as giving developers the opportunity to change a test’s regulatory status by having it evaluated via the recently launched interagency serological test validation program spearheaded by NCI (see “NCI Takes Lead on Serological Tests”).
“We encourage all serology point-of-care developers to participate. It’s a voluntary program but that would be most helpful I think to everyone,” he said.
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Editor’s note: This story was updated on April 16 at 12 p.m. PT