FDA reports on serological test validation and education efforts

April 21, 2020

“Given the active dialogue about serological tests, also known as antibody tests, that are currently on the market, and their significance in the nation’s response efforts, we’d like to provide further details about our thinking on these tests and our approach to making accurate and reliable serology tests widely available, while also protecting Americans from tests marketed with false or unsubstantiated claims,” says Stephen M. Hahn M.D., Commissioner of Food and Drugs for the US Food and Drug Administration (FDA) in a recent statement. 

He continued, “Results from these tests can help identify who has been infected and developed antibodies that may protect from future infection as well as identify those still at risk. Results can also help inform who may qualify to donate blood that can be used to manufacture convalescent plasma, an investigational product for use with those who are seriously ill from COVID-19. 

First, we continue to provide the opportunity for interested developers to request FDA authorization through the emergency use authorization (EUA) process. To date, we have already issued four EUAs for serological tests, and we expect that number to continue to grow in the coming weeks. The FDA encourages developers to submit EUA requests for their tests, as an EUA will provide laboratories and providers with assurance that FDA has reviewed that test. We are working around-the-clock to review EUA submissions quickly and we continue to take steps to ensure the process is as streamlined and efficient as possible. For example, we are working on EUA Templates that laboratories and commercial manufacturers may use to facilitate the preparation and submission of an EUA request. We expect to make them available in the coming days. 

To enhance the U.S. Government’s ability to identify well-performing tests and inform FDA recommendations and decision making, we are collaborating with the National Institutes of Health’s National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID) and the Centers for Disease Control and Prevention (CDC) to establish a capability at NIH to evaluate serological tests for developers. This effort includes tests already available for use, as well as tests not yet on the market where additional validation data is needed to support an EUA. Performance assessments for serological tests will begin soon, and we expect to start seeing results shortly thereafter. We will review NIH’s results expeditiously, and performance results from NIH’s assessment may complement and inform the determination of whether FDA issues an EUA for a particular test. 

Recognizing that more flexibility was needed during a pandemic of this scale and speed, and incorporating feedback from the medical community, states and test developers, we have also provided regulatory flexibility for serological tests in an effort to provide laboratories and health care providers with early access to these tests with the understanding that the FDA had not reviewed or authorized (or “approved”) them, at least not initially, and these tests should not be used for diagnosing or excluding active SARS-CoV-2 infection. 

Specifically, last month, as part of our broader strategy, the FDA issued a policy explaining that FDA does not intend to object when developers of serological tests market or use their tests without prior FDA review where: 

1) the tests are validated by the developer to determine that they are accurate and reliable,

2) notification of the developer’s validation is provided to FDA, and

3) the tests are labeled appropriately, including that they are not to be used as a sole basis for diagnosis. Our 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. 

The policy does apply to tests that can be performed in patient care settings. 

Laboratories could validate tests they receive from commercial manufacturers and determine if they should be used in their facilities. Some laboratories have already done so or have developed their own serological tests. 

The bottom line is that FDA still expects tests to be validated even under our revised policy for tests. However, the EUA process or an evaluation by NIH supports greater confidence in test performance. 

Unlike a test designed to diagnose an active COVID-19 infection (specifically from the SARS-CoV-2 virus), serological tests can help identify individuals who have developed an immune response to the virus, either as part of an active infection or a prior infection. The tests detect the presence of antibodies in the blood – if antibodies are present, that indicates that the person has been exposed to the virus and developed antibodies against it, which may mean that person has at least some immunity to the coronavirus. 

In the early days of an infection when the body’s immune response is still building, antibodies may not be detected, which is why serological tests should not be used as the sole basis to diagnose or exclude infection with the SARS-CoV-2 virus. 

There is still a great deal about COVID-19 immunity that we don’t yet fully understand. For example, we don’t yet know that just because someone has developed antibodies, that they are fully protected from reinfection, or how long any immunity lasts. We do expect that data from more widespread serological testing will help us track the spread of the virus nationwide and assess the impact of our public health efforts now, while also informing our COVID-19 response as we continue to move forward. Determining the next steps in our response to COVID-19 is partially dependent on an accurate assessment of our national efforts thus far, and the quality of data for making this decision is dependent on accurate testing products.  

All clinical tests should be validated prior to use, and this expectation is articulated in our March 16 policy. We have provided regulatory flexibility regarding the independent check by FDA for antibody tests that are limited in their clinical applications, but still expect all developers to validate their tests prior to offering them for limited clinical uses.  

To minimize the number of false positive results, serological tests must be well-designed to specifically identify antibodies against SARS-CoV-2 and must not “cross-react,” or provide positive results when encountering antibodies against other respiratory viruses. 

Currently, we are working on several fronts to provide more clarity about which tests have received FDA review and which have not. In addition, to facilitate awareness of these serological tests, the FDA has been posting on its website the tests for which it has received a notification under this policy since mid-March. We have also updated our website to better clarify which tests have been authorized by FDA and which have not been authorized. However, some test developers have misused the serology test kit notification list to falsely claim their serological tests are FDA approved or authorized. Others have falsely claimed that their tests can diagnose COVID-19. When we become aware of these issues, we have and will continue to take appropriate action against firms making or distributing unvalidated tests or those making false claims, such as issuing Warning Letters requesting that companies stop their unlawful promotion and detaining and refusing fraudulent test kits at the border. 

We are sharing educational materials with state governments, hospital systems, payors, and health care professional associations to ensure they understand the potential for false-positive results in tests that have not yet been reviewed by FDA, and can make educated decisions when considering purchasing, insuring and using these tests. We have been and will continue actively engaging with the testing development community to continue to gain input and provide clarity around our processes, policies and validation efforts.” 

FDA has the statement.  

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