The FDA has revised its emergency use authorization (EUA) policy for testing for the COVID-19 pandemic, the impact of which falls principally on serological tests for antibodies generated by the SARS-CoV-2 virus. The agency had previously allowed a commercial antibody test developer to distribute a test without submitting the validation data, but makers of such tests now must forward the validation data to the FDA within 10 days, a move prompted in part by inappropriate claims made by some test developers.

The FDA’s initial policy was published March 16, but the latest announcement by the FDA notes that the initial policy was driven largely by a need to develop answers to “critical population-level questions” regarding prevalence. The statement notes that 12 antibody tests have been authorized under the EUA policy, while another 200 are either under review for a completed EUA filing or a pre-review process for such a filing.

FDA commissioner Stephen Hahn said in a May 4 press briefing that in addition to the 10-day turn-around policy, the agency is offering templates that can be used for EAU submissions, one each for commercial tests and for tests developed by labs that certified to conduct high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988. Hahn cautioned that a single serological test is, in his view, inadequate to certify an employee for returning to work. He said also that the underlying question of whether the presence of antibodies confers immunity has still not been clearly answered.

Jeff Shuren, director of the agency’s Center for Devices and Radiological Health, said the EUA process now includes a triage check for new filings, and that any such filings that raise concerns will be examined first. EUAs that seem to bear well-documented and sturdy validation data would be examined after the more concerning submissions have been processed.

The FDA is aware that a number of companies are inappropriately marketing their serological tests, some of which have been marketed for use at home, while others have illegitimately claimed that the developer acquired an EUA authorization. Some of these have been referred for criminal investigation, while other developers were required only to modify the claims. Several tests have been detained either at the border or at port of entry.

Policy is immediately in effect

The May 4 policy document, labeled as an immediately-in-effect (IIE) policy, provides guidance on tests that are developed under state authority, also a provision of the agency’s antecedent March 16 policy document. The FDA said the state regulation policy is generally “unchanged from the initial publication” of the guidance from Feb. 29, 2020, adding that the initial policy has been successful in encouraging development of serological tests. Developers of commercial serological tests for antibodies such as immunoglobulins G and M enjoy only 10 days of discretion between full validation/notification of the test and filing of an EUA submission. The presumption here is that tests that are commercially developed for distribution present a greater hazard than lab-developed tests (LDTs) due to the broader potential use. However, an LDT that falls into this category of test type and conditions may also be subject to de-listing from the FDA website as well as “additional actions as indicated” if the performance of that test is faulty.

The agency said it is encouraging administrators of clinical labs to file EUA documentation for serological antibody tests developed in clinical labs for use only in that lab. This was described as “a reasonable period of time” for preparing a submission for post-validation documentation. Failure to do so will result in removal of that lab from the FDA list of labs, but the agency said it “may take additional actions as appropriate.”

The IIE policy further urges lab operators to provide the agency with information on test capacity. The FDA will work with lab test developers to address any EUA requests seen as problematic, including by means of labeling changes and technical assistance with bench testing.

Clinical labs are at liberty to run a test when paired with new specimen types without notifying the agency, so long as the test is correspondingly validated. Another requirement for this scenario is that the specimen type was already included in another EUA, however. An amended EUA filing is not necessarily required for other types of modifications to an EUA-authorized test if the lab employs a bridging study. The agency recommends that such a study make use of three-fold serial dilutions of viral materials in a pooled respiratory sample matrix, but the modified test must reach the same limits of detection as the index test on which it is based.

The FDA also posted a webpage spelling out the performance parameters for a number of serology tests, although the agency again cautioned that the general prevalence of COVID-19 in the U.S. is unknown, thus affecting the reliability of a serology test as a surveillance instrument. The test validation partnership between the FDA, NIH and CDC is employing nucleic acid amplification to validate the results of submitted serology tests.

Diagnostic tests still on 15-day turn-around

The IIE document notes that makers of diagnostic rather than surveillance test kits still have 15 business days to file an EUA for a test that has been validated. Developers whose diagnostic tests are running into problems can expect the same advice from the FDA regarding labeling and bench testing as spelled out for serology/antibody tests.

Validation for molecular tests should control for cross-reactivity via wet testing, although the agency will accept an in silico evaluation for cross-reactivity to the MERS-coronavirus. The section dealing with antigen testing calls for validation for limits of detection, cross-reactivity and microbial interference.

Julie Khani, President of the American Clinical Laboratory Association, told BioWorld that the association was still reviewing the latest FDA announcement, but that the ACLA “commend[s] the agency for its continued diligence in evaluating the available data regarding testing options and implementing policies that promote the public’s health.” She said ACLA will continued to work with the administration “to expand the availability of high-quality tests nationwide.”

The FDA has revised its emergency use authorization (EUA) policy for testing for the COVID-19 pandemic, the principle impact of which falls on serological tests for antibodies generated by the SARS-CoV-2 virus. Instead of allowing a commercial test developer 15 business days to forward a test validation study’s results to the agency, that deadline has been tightened to 10 days, a move prompted in part by inappropriate claims made by some test developers.

The FDA’s initial policy was published March 16, but the latest announcement by the FDA notes that the initial policy was driven largely by a need to develop answers to “critical population-level questions” regarding prevalence. The statement notes that 12 antibody tests have been authorized under the EUA policy, while another 200 are either under review for a completed EUA filing or a pre-review for such a filing.

FDA commissioner Stephen Hahn said in a May 4 press briefing that in addition to the 10-day turn-around policy, the agency is offering templates that can be used for EAU submissions, one each for commercial tests and the other for tests developed by labs certified to conduct high-complexity tests under CLIA. Hahn cautioned that a serological test is, in his view, inadequate to certify an employee for returning to work. He said also that the underlying question of whether the presence of antibodies confers immunity has still not been clearly answered.

Jeff Shuren, director of the agency’s Center for Devices and Radiological Health, said the EUA process now includes a triage check for new filings, and that any such filings that raise concerns will be examined first, while EUAs that seem to bear well-documented validation data would be examined after the more concerning submissions have been processed.

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