With the spread of COVID-19, healthcare providers—including those that are more easily accessible to patients, like primary care practices and urgent care clinics—are looking for fast and reliable tests to diagnose infection. It is no wonder, then, that many providers are contemplating the use of serological or “antibody” tests (i.e., tests that measure the number of antibodies present in the blood when the body is responding to a specific infection, like COVID-19), which the Food and Drug Administration (FDA) has characterized as “less complex” than other, more sophisticated molecular tests. And the demand for antibody tests will no doubt rise following New York Governor Andrew Cuomo’s announcement over the last couple of days of a statewide, antibody testing survey by the New York Department of Health that began on Monday, April 20.

However, despite the appeal of antibody tests—easy to administer, and rapid results—and although the Centers for Medicare & Medicaid Services (CMS) has relaxed enforcement of certain requirements under the federal Clinical Laboratory Improvement Amendments (CLIA) program, providers still need to obtain proper authorization to provide the testing, and unfortunately a CLIA Certificate of Waiver does not appear to be sufficient. However, guidance on this and so many other healthcare regulatory matters is changing almost daily and the use of serology or antibody tests continues to be a topic of conversation at FDA Town Halls, so stay tuned for potential updates.

CLIA Certification, Generally

Under the federal CLIA program, administered by CMS, no person can conduct laboratory testing unless the person has been issued a CLIA certificate (or a state equivalent, for CLIA-exempt states) authorizing that category of examination. Broadly speaking, tests are categorized as either “waived” or “non-waived,” and the latter category breaks down further into tests of high complexity or moderate complexity. While CMS is responsible for issuing certificates and enforcing compliance under the CLIA program, the FDA determines CLIA categorization of tests in connection with a manufacturer’s application for marketing approval. So-called “waived” tests are effectively tests that are so simple and accurate as to render the likelihood of erroneous results negligible, or the tests pose no reasonable risk of harm to the patient if the test is performed incorrectly. If a test is not waived, the FDA will designate it with a complexity level using a “scorecard” system.

A provider holding a CLIA Certificate of Waiver may, of course, only perform those tests that have been deemed waived. Anything more requires a higher level of CLIA certification.

Emergency Use Authorizations

In the event of a declaration of a public health emergency or similar threat by the Secretary of the Department of Health and Human Services (HHS), the FDA may allow unapproved medical products, or unapproved uses of approved medical products, to be used to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by chemical, biological, radiological, and nuclear (CBRN) agents, including emerging infectious disease, when there are no adequate, approved, and available alternatives. In the context of laboratory tests, this means the FDA may issue emergency use authorizations (EUA) for tests that have not yet been CLIA-categorized, and approve the use and distribution of such tests on an expedited basis.

On February 4, the HHS Secretary indeed declared a public health emergency because of the COVID-19 outbreak. The FDA subsequently began accepting requests from laboratories that meet the CLIA regulatory requirements to perform high-complexity testing and commercial manufacturers for EUA authorization to perform and distribute diagnostic tests to detect the “SARS-CoV-2” virus, the virus underlying the COVID-19 disease. EUAs issued to manufacturers seeking to distribute such tests designate the settings authorized to accept and perform them: for example, (1) laboratories CLIA-certified to perform high and/or moderate complexity tests, and/or (2) point of care settings, which are deemed to be CLIA-waived. The FDA confirms in its FAQs on Diagnostic Testing for SARS-CoV-2 that ultimately ‘“when the FDA authorizes point of care tests (including SARS-CoV-2 point of care test systems) under an EUA, such tests are deemed to be CLIA waived tests.” The FDA also confirms in the same FAQ that point of care settings include settings such as physician offices, urgent care clinics, and hospitals.

Interestingly, in the FDA’s March 26 guidance, the FDA indicates that EUA authorization is generally not necessary for serological or antibody testing—at least in those instances where the test will not be used as the sole basis to diagnose infection status—and that the FDA will not object to the distribution and use of such tests if they have been validated, notification is provided to the FDA, and the following disclaimer is included in the test reports:

• This test has not been reviewed by the FDA.
• Negative results do not rule out SARS-CoV-2 infection, particularly in those who have been in contact with the virus. Follow-up testing with a molecular diagnostic should be considered to rule out infection in these individuals.
• Results from antibody testing should not be used as the sole basis to diagnose or exclude SARS-CoV-2 infection or to inform infection status.
• Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.

Serology Tests without EUA Authorization Categorized as High Complexity by Default

Due to the fact that antibody tests may be distributed by manufacturers, and performed by labs, without EUA authorization, providers have been understandably uncertain as to whether they may offer the test under a CLIA Certificate of Waiver. However, the FDA’s FAQs clearly state that “[t]ests being offered prior to or without an EUA under the policies outlined in the FDA’s Policy for Diagnostic Tests for Coronavirus Disease-2019 that have not yet been reviewed by the FDA, are not FDA authorized, and have not received a CLIA categorization.” The guidance goes on to note that while “such tests may be appropriate for use in clinical laboratories and by healthcare workers at the point of care, the policies in the Policy for Diagnostic Tests for Coronavirus Disease-2019 do not provide a CLIA categorization and do not override any CLIA requirements.” Accordingly, and consistent with CLIA rules, tests—including antibody tests—offered under the FDA’s recent policies “are considered high complexity by default until or unless they are authorized and deemed to be appropriate, through an EUA authorization or general FDA review processes, to be performed as moderate or waived complexity tests.”

There is no doubt that CLIA certification is required to perform COVID-19 testing. This much is confirmed by CMS’ March 26 guidance. Further, in the absence of an EUA to the contrary, serology or antibody tests identifying antibodies to SARS-CoV-2 from clinical specimens, including those for which no EUA authorization is necessary (because they will not be used as the sole basis to diagnose infection status), should be viewed as high complexity tests, and therefore may not be administered at point of care settings where the provider is operating under a waiver certificate only. As of the date of this publication, the FDA has issued only four EUAs for test kits using serological testing, all of which limit the use of such tests to laboratories certified to perform high or both moderate and high complexity tests. To the extent a provider is qualified to use such tests, the provider should confirm that the manufacturers of such tests have fully complied with the notification and disclaimer conditions described above.

Recommendations for Healthcare Providers

In this time of uncertainty, and when so many other federal and state requirements related to the delivery of healthcare are being relaxed or waived altogether, it is easy to understand why so many point of care providers would contemplate the use of the easy-to-use, low complexity antibody tests which have been likened to pregnancy tests insofar as the manner in which they are administered. Nonetheless, the prudent provider should appreciate that the risk of non-compliance under CLIA remains very real, and the penalties for non-compliance—namely, for performing a lab test which is not within the category of lab tests authorized by a provider’s CLIA certificate—could result in, among other things, suspension, limitation or revocation of the provider’s certificate; cancellation of a laboratory’s approval to receive Medicare payment for services; and, for intentional violations, even imprisonment of the offending party.