Serology tests could play a critical role in the fight against COVID-19. Serology tests may help determine who can donate convalescent plasma—a part of the blood containing antibodies—which is currently being explored as an investigational treatment for those with COVID-19. Convalescent plasma has been studied in outbreaks of other respiratory infections as well, including the 2003 SARS and 2012 MERS epidemics. Recognizing this, FDA updated guidance regarding convalescent plasma on Friday.
As serology tests measure the amount of antibodies present in the blood when the body responds to an infection such as COVID-19, they may also help identify individuals who have developed an immune response. Coupled with other data, this could inform employers’ return-to-work strategies, a topic we analyzed here (noting that, thus far, EEOC only endorses testing employees to “determine if they have the virus” and has not addressed testing for antibodies to the virus). But despite this early optimism and much press about antibody tests, more scientific evidence is needed. For example, the World Health Organization last month released a clear statement on the current state of the science: “[T]here is not enough evidence about the effectiveness of antibody-mediated immunity to guarantee the accuracy of an ‘immunity passport’ or ‘risk-free certificate.’”
During a Public Health Emergency such as the COVID-19 crisis, FDA can use emergency authorities, including EUAs, to accelerate the availability of medical products by allowing unapproved products to reach patients in need when there are no adequate, FDA-approved alternatives, a process we described here. These products can include tests to diagnose diseases, drugs to treat or prevent life-threatening conditions, and medical devices otherwise needed in the context of a public health crisis. FDA has maintained a fairly relaxed policy for serology tests in the COVID-19 crisis, since mid-March, permitting commercial antibody tests to be marketed and used without FDA EUA review if the test is labeled clearly that is it not the sole diagnostic for COVID-19, among other things. That policy does not apply to at-home specimen collection or at-home testing because of the added challenges in assuring test accuracy that these pose, as we have previously reported.
Recently, a congressional subcommittee criticized FDA for “fail[ing] to police” the coronavirus serological antibody test market. Although the agency has been actively monitoring the market for fraudulent COVID-19 products, a topic we have analyzed repeatedly, the subcommittee found that “[n]umerous companies appear to be marketing fraudulent tests.”
In response, FDA stated in its updated policy on testing: “FDA’s policy was based on the considerations that serology tests are not meant to diagnose active SARS-CoV-2 infection and that early availability and use of these tests could help answer critical questions about the prevalence of COVID-19 infections in different communities, whether the presence of antibodies conveys immunity, and, if so, for how long. That policy succeeded in encouraging development of serology tests.”
By April 7, over 70 test developers had notified FDA that they had validated serology tests available for use but were not seeking an EUA. However, FDA has authorized a dozen EUAs. At present, FDA policy regarding serological antibody tests has three distinct features:
- Validating Tests. FDA announced in late April that it is collaborating with the National Institutes of Health (NIH) to establish a capability at NIH to evaluate serology tests for developers. In short, any serology test seeking an EUA should meet NIH standards for validation and submit its test to NIH for independent verification, which FDA will use in its EUA decision process.
- Requiring EUA for Commercial Manufacturers. FDA revised its Policy for COVID‑19 Tests during the Public Health Emergency (first issued in February and revised in March) this week. FDA reversed course and now requires that commercial manufacturers of antibody tests submit EUA requests along with their validation data within 10 business days from the date they notified FDA of their validation testing or from the date of this policy revision, whichever is later. The prior list of antibody tests that had submitted notification to FDA of validation (but which were not seeking an EUA) has been removed from the FDA website and is no longer available. It is our understanding that all commercial manufacturers of serology tests that had provided such notice to FDA must submit an EUA to FDA by May 20, or those serology tests will be considered unauthorized products. This is presumably why the list of “notified” serology tests has now been removed from the public FDA website.
- Laboratories certified by CLIA to perform high complexity tests may continue to develop and use antibody tests without an EUA from FDA, but FDA does encourage even labs to consider submitting an EUA.
- Including Warning Labels. Last month, FDA warned that some firms were falsely claiming their serology tests were approved by FDA. The agency advised that it will take appropriate action against firms making false claims, which could include removing products from the market or referring them to criminal investigators. It repeated this admonition Monday.
Ultimately, FDA is requiring commercial manufacturers to submit EUA requests for their serology tests, as an EUA will assure laboratories and providers that FDA has reviewed that test. The agency is working around the clock to review EUA submissions and ensure this process is streamlined and efficient. In fact, it recently created EUA Templates for test kit manufacturers and laboratories to facilitate submission of an EUA for a serology test. But as an added measure, it has begun providing performance threshold recommendations for specificity and sensitivity to the serology tests it has authorized.
The FDA guidance outlined above works in tandem with the Public Readiness and Emergency Preparedness (PREP) Act—as expanded by the Coronavirus Aid, Relief, and Economic Security (CARES) Act—and corresponding guidance from the U.S. Department of Health & Human Services (HHS) and Office of the Assistant Secretary for Health (OASH), an agency within it. HHS issued an omnibus advisory opinion regarding PREP Act immunity, which we summarized here. As an Authority Having Jurisdiction under the PREP Act, OASH then extended this immunity to licensed pharmacists, authorizing them to order and administer serology tests that FDA has “authorized.” By doing so, such pharmacists will qualify as “covered persons” under the PREP Act and may receive immunity with respect to claims for loss caused by, arising out of, relating to, or resulting from the use of such tests.
Although OASH included a footnote to FDA’s Emergency Use Authorizations, it did not state whether Prep Act immunity was premised on obtaining an EUA. We would argue it was not. At that time, FDA policy specifically allowed serology tests to be marketed and used if the test developers provided notice of validation to FDA. Before the policy reversal, “authorized” serology tests could have included those tests listed on FDA’s website as having submitted notice of validation, whether or not they were submitting EUA requests. Further, when OASH issued its guidance on April 8, FDA had only granted one EUA; therefore, this guidance could not “rapidly expand COVID-19 testing across America” if it was referring to a single test. Still, FDA’s revised policy requiring EUAs for all serology tests creates uncertainty, and neither HHS nor OASH appear to have issued new guidance regarding serology tests since FDA reversed course. We encourage anyone evaluating potential PREP Act immunity to consult legal counsel. In addition, the Morrison & Foerster COVID-19 Task Force will continue to provide updates to consumer-facing product manufacturers as agencies issue new guidance.