Big Changes in FDA’s Serology/Antibody Testing Requirements

The new Guidance can be found here.

The FDA’s oversight and regulation of the “regular” diagnostic test process remain pretty much the same. The new Guidance provides only very minor “process updates and clarifications,” which do not affect what the FDA said in those earlier Guidances, which we described in our previous Alert.

However, the big change involves the FDA regulation of Serology/Antibody tests. As most readers of these Alerts will know, serology/antibody tests have been developed to understand a person’s and the population’s exposure to COVID-19. A person who has been exposed to, and recovered from, COVID-19 will likely have antibodies to the SARS-CoV-2 virus in his/her blood. These tests may be important for guiding the next steps in the fight against the pandemic, such as by providing information on disease prevalence and the frequency of asymptomatic infection, and also by identifying potential donors of “convalescent plasma,” an approach in which blood plasma containing antibodies from a recovered individual serves as a therapy for an infected patient with severe or immediately life-threatening disease.

FDA says that the earlier Guidances were issued to promote flexibility in allowing serology/antibody tests to come to market earlier. However, in the terms of the FDA:

[F]lexibility never meant we would allow fraud. We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety. Some test developers have falsely claimed their serological tests are FDA approved or authorized. Others have falsely claimed that their tests can diagnose COVID-19 or that they are for at-home testing, which would fall outside of the policies outlined in our March 16 guidance, as well as the updated guidance. Also, since that time, the FDA has become aware that a concerning number of commercial serology tests are being promoted inappropriately, including for diagnostic use, or are performing poorly based on an independent evaluation by the NIH.

To remedy this, the FDA is now requiring all commercial manufacturers who have been marketing serology/antibody tests (and the Agency says there are over 200 of them) to submit Emergency Use Authorization (EUA) requests, with their validation data, within 10 business days from the date they notified the FDA of their validation testing or from the date of this policy (May 4, 2020), whichever is later. (This new policy does not affect the 12 companies that have already obtained EUA approval for their serology/antibody tests.)

Under the old Guidances, commercial manufacturers only had to validate their tests, notify the FDA that the tests have been validated, and comply with certain labeling restrictions. Now an EUA is required from both existing and new manufacturers. And FDA says that if an EUA request is not submitted within 10 days, it will remove the manufacturer/test from its website listing of notified tests and may very well take additional regulatory action. As part of the Guidance, FDA is providing a “Serology Template for Manufacturers” that establishes new and strict specific performance threshold “recommendations” for specificity and sensitivity for all serology test developers.

This new EUA requirement does not apply to tests from laboratories that are certified under the Clinical Laboratory Improvements Amendments (CLIA) to perform high-complexity testing. FDA says that, for those tests, it does not intend to object to the development and use of serology tests to identify antibodies to SARS-CoV-2 by laboratories that are certified under CLIA to perform high-complexity testing, where the test has been validated, notification is provided to FDA, and certain information is included in the test reports. This is close to what FDA allowed under its old policy, though as part of the Guidance, FDA provides a Template for those laboratories that want to submit an EUA for their test. The Agency is encouraging these labs to submit an EUA.

In the new Guidance, FDA is also being much clearer about home testing and home specimen collection, which have been the subject of much discussion and speculation in the press. FDA is clarifying that unless and until an EUA is issued that authorizes home testing and home specimen collection, no test can be used in the home. Instead, unless an EUA specifically authorizes otherwise, use of those tests is limited to laboratories certified to perform high complexity testing, and at the point-of-care when covered by the laboratory’s CLIA certificate for high-complexity testing. And FDA reiterates that this policy “does not apply to at-home testing, including at-home specimen collection, due to additional considerations that require FDA review.”

The “additional considerations” are set forth in footnote 16 of the Guidance, which says:

Different risks are presented with specimen collection in the home versus healthcare setting. Home collection raises several issues of importance, including whether the lay user can safely and properly collect the specimen, whether the components of the specimen transport media are safe for use in the home environment (since some may be toxic), proper shipment, and adequate stability of the specimen given the time lapse between collection and testing and the potential impact of shipping conditions (such as, if the specimen sits in a hot truck). Tests that are also interpreted in the home require demonstration of the ability of a lay user to collect their specimen, run the test, and interpret their results accurately.