Q&A column, 7/17

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Editor: Frederick L. Kiechle, MD, PhD

Submit your pathology-related question for reply by appropriate medical consultants. CAP TODAY will make every effort to answer all relevant questions. However, those questions that are not of general interest may not receive a reply. For your question to be considered, you must include your name and address; this information will be omitted if your question is published in CAP TODAY.

We devote the full column this month to a question about Emergency Use Authorization tests and specifically a test issued under EUA for detecting Zika virus infection.

Q. A laboratory is considering the implementation of a laboratory test for the diagnosis of Zika virus infection. This test is currently labeled as a test under the issuance of an Emergency Use Authorization. What specific regulations regarding the use of this test, quality control, and proficiency testing apply when performing this test on patient specimens?

A. To answer this question, I will first discuss the Emergency Use Authorization (EUA) process in general and provide background on how the Food and Drug Administration uses it. I will then discuss the specific regulations and requirements for implementing a test issued under EUA for detection of Zika virus infection in patient specimens.
EUA process. The EUA is a legal mechanism under sections 564, 564A, and 564B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) by which the FDA can allow the following:

•  use of an unapproved medical product (e.g. diagnostic device, drug, or vaccine) or

•  the unapproved use of an approved medical product during an emergency for the diagnosis, treatment, or prevention of a serious, life-threatening illness caused by chemical, biological, radiological, and nuclear (CBRN) agents, including emerging infectious diseases.

In the situation described above, a Zika virus test is an unapproved medical product for detection of Zika virus RNA in clinical specimens such as serum and urine. With the Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA) of 2013, amendments to the EUA authority enabled the FDA to further help strengthen the nation’s public health protections against CBRN threats by facilitating the availability of medical countermeasures (e.g. drugs, vaccines, and diagnostic devices) during public health emergencies.

Of note, the use of a medical product under the EUA authority is, however, distinctly different from the use of a medical product under an investigational application, such as an Investigational New Drug Application or Investigational Device Exemption, for which different regulations apply. The objective of the IDE/IND is to assess efficacy and safety of the investigational medical product while ensuring the protection of the human subjects during the research of such product. Institutional Review Board (IRB) approval; written, signed, and witnessed informed consent; adverse event monitoring and reporting; and protocol training of all study personnel are required components of IDE/IND protocols. However, for Emergency Use Authorizations, IRB approval, informed consent, and specific protocol training are typically not required.

Situations in which FDA issues an EUA. The FDA’s issuance of an EUA is predicated on the declaration of an emergency by the secretary of the Department of Health and Human Services that justifies the authorization of emergency use for a medical product. Such declaration is based on one of four scenarios:

• determination of the existence of or the potential for a domestic emergency by the secretary of the Department of Homeland Security;
• determination of the existence of or the potential for a military emergency by the secretary of the Department of Defense;
• determination of the existence of or the potential for a public health emergency by the secretary of the Department of Health and Human Services; or
• identification by the secretary of the Department of Homeland Security of the existence of a significant threat to the national security and/or the health and security of U.S. citizens living abroad.

Based on the declaration of one of these four scenarios, and after additional consultation by the Office of the Assistant Secretary for Preparedness and Response, the director of the National Institutes of Health, and the director of the Centers for Disease Control and Prevention, the commissioner of the FDA may issue an EUA. Ebola virus and H1N1 (2009) Influenza A are examples of significant infectious threats that have resulted in the issuance of an EUA.

At the point of declaration of a significant emergency or threat, the issuance of an EUA also requires that the following four statutory criteria have been met: