Introduction

The number of cases of SARS-CoV-2 coronavirus infection, and COVID-19, the disease caused by the virus, continue to increase in the United States—both in number and in location (real-time map). At the same time, the number and severity of symptoms post-infection can vary by age and other risk factors (CDC Report). High level officials and politicians have been reported to be infected by, or in contact with, the virus.

COVID-19 diagnostic tests are crucial to helping to curb the spread of COVID-19, and to accurately triage patients who may have similar symptoms, but different diseases (e.g., COVID-19 and influenza). However, COVID-19 diagnostic tests remain in short supply in the U.S.

One path for bringing COVID-19 diagnostic tests to market in a public health emergency is through emergency use authorization (EUA). Under Section 564 of the Federal Food, Drug, and Cosmetic Act (FDCA), and subsequent legislation, the U.S. Food and Drug Commissioner may "authorize the introduction into interstate commerce … a device [e.g., a diagnostic test] … intended for use in an … emergency … that is not approved, licensed, or cleared …"

Put simply, if a declaration of emergency has been issued, and a COVID-19 diagnostic test developer, after validation and other appropriate steps, obtains an individual EUA, the test developer can market its COVID-19 diagnostic test in the U.S.—assuming continued compliance with the FDCA and related federal and state laws and regulations (for example, CLIA). Marketing a COVID-19 diagnostic test under an EUA can continue until the individual test developer's EUA is directly or indirectly revoked.

The EUA process, however, has, created difficulties in bringing some diagnostic tests to market in the U.S. To help facilitate bringing COVID-19 diagnostic tests on-line, the U.S. Food and Drug Administration (FDA), recently issued a statement and a guidance. The statement, from Stephen Hahn, commissioner of food and drugs, notes the policy set forth in the guidance is "unprecedented" and will help "expand the number and variety of diagnostic tests, as well as available testing capabilities in health care settings, and reference and commercial laboratories." So, what is contained in the guidance? We address relevant guidance policies below.

1. State Authorization of Laboratories Certified Under CLIA That Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing

An important policy of the guidance allows a state to authorize laboratories within the state to offer COVID-19 diagnostic tests. "A state, under the authority of its own state law, can authorize laboratories within the state to develop and perform a test for COVID-19 under a process that the state establishes." […] "FDA does not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA, and where instead the state or territory takes responsibility for COVID-19 testing by laboratories in its state during the COVID-19 outbreak."

The FDA notes it will "not be reviewing the process adopted by the State," and the FDA expects that such "states as part of their oversight process will require laboratories developing SARS-CoV-2 tests to validate those tests prior to use." The FDA also encourages laboratories that develop and perform a test for COVID-19 under this policy to notify the FDA that they have started clinical testing by sending an email to that effect to CDRH-EUA-Templates@FDA.HHS.GOV.

"It would be helpful to FDA if laboratories provide information on testing capacity." This will help the FDA "monitor the landscape" … "to ensure adequate testing capacity across the country."

Thus, states can now authorize the performance of COVID-19 diagnostic tests under state law, as an alternative to the FDA test development pathways. Developing a test under state authorization may also have advantages over EUA COVID-19 diagnostic tests when, eventually, EUA revocation occurs.

2. Laboratories Certified Under CLIA That Meet the CLIA Regulatory Requirements May Perform High-Complexity Testing Using Their Validated Tests Prior to EUA Submission

The guidance policy under this section applies to laboratories—certified under CLIA to perform high-complexity testing—that seek to develop and perform diagnostic tests to detect the SARS-CoV-2 virus and pursue EUA authorization from FDA (EUA CLIA Labs). The FDA notes that "for a reasonable period of time after validation and while they are preparing their EUA requests, FDA does not intend to object to the use of these SARS-CoV-2 tests for specimen testing." In essence, and subject to certain conditions, EUA CLIA labs, after validation, can begin to offer their SARS-CoV-2 tests.

The FDA sets guidelines, noting that "15 business days is a reasonable period of time to prepare an EUA submission for a test that has already been validated;" that all clinical tests should be "validated prior to use;" and that the FDA should be notified following completion of assay notification by email at DRH-EUA-Templates@FDA.HHS.GOV. The FDA also notes it would be "helpful to FDA if laboratories provide information on testing capacity."

Thus, the guidance appears to set a 15-business day limit from when the COVID-19 diagnostic is provisionally offered, and EUA submission. Along these lines, the FDA "has made available, through download from our website, a template that laboratories may choose to use to facilitate the preparation, submission, and authorization of an EUA." Soon after receiving the EUA request, "FDA intends to perform a preliminary review to identify if there are any problems with the performance data." If a problem is identified, the FDA "intends to work with the laboratory to address the problem (e.g., through labeling or bench testing)."

The ability to provisionally offer the COVID-19 diagnostic tests comes with a potential downside. If any diagnostic test problems are significant and cannot be addressed in a timely manner, "FDA would expect the laboratory to stop testing and issue corrected test reports indicating prior results may not be accurate."

Also, if the FDA is not able to authorize an EUA, the FDA will notify the laboratory. If the FDA cannot authorize the EUA, the FDA would expect the laboratory to stop testing and issue corrected test reports indicating prior test results may not be accurate. The FDA does not intend to object to the use of a test, without a new or amended EUA, where the test is validated using a bridging study to an EUA-authorized test.

Finally, while awaiting FDA determination on the EUA request, the FDA "recommends that clinical laboratories obtain confirmation of the first five positive and the first five negative clinical specimens using an EUA-authorized assay, which may involve sending these ten specimens to another laboratory for confirmation. If any of these results cannot be confirmed, the laboratory should notify FDA at CDRH-EUA-Templates@FDA.HHS.GOV, and take other appropriate action" such as "terminating testing patient specimens, and issuing a corrected test report that indicates the prior test result may not be valid."

Thus, under this policy, selected laboratories can provisionally offer validated tests for 15 business days before EUA submission, but if, after EUA submission, the FDA determines there are non-correctable problems, or an EUA cannot be issued, the test manufacturer must terminate patient testing and issue corrected reports indicating that prior tests may not be valid.

3. Commercial Manufacturer Development and Distribution and Laboratory Development and Use of Serology Tests Without an EUA

The policy applies to developers of serology tests that identify antibodies (e.g., IgM, IgG) to SARS-CoV-2 from clinical specimens. The FDA note this policy is limited to testing in laboratories or by healthcare workers at the point-of-care. This policy does not apply to at home testing.

Serological tests are less complex than molecular tests and are solely used to identify antibodies to the virus, the FDA does not intend to object to the development and distribution of serological tests—by commercial manufacturers or development and use by laboratories of serology tests to identify antibodies to SARS-CoV-2—where the test has been validated, notification is provided to FDA, and information along the lines of the following is included in the test reports: This test has not been reviewed by the FDA.

The FDA notes that negative results do not rule out SARS-CoV-2 infection, particularly in those who have been in contact with the virus; that follow-up testing with a molecular diagnostic should be considered to rule out infection in these individuals; and that 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.

Separately, the FDA recommends that "developers planning to submit an EUA for serological testing as the sole basis to diagnose or inform infection status, include information along the lines of the statements above in their test reports until data is submitted and an EUA is authorized for additional uses."

Finally, the guidance also offers validation recommendations for different types of COVID-19 diagnostic tests.

Conclusion

The FDA's immediately-in-effect guidance offers three importation options for COVID-19 test developers: state authorization; the ability to provisionally go to market for a limited time before EUA submission; and the ability to offer serology tests without an EUA. These policies should help to increase the availability of COVID-19 diagnostic tests. 

Charles Andres contributed to the preparation of this Wilson Sonsini alert.