Emergency Use Authorization and Enforcement
FDA Response to COVID-19 – Introduction & Background
In response to the outbreak of the novel coronavirus (SARS-CoV-2) causing the disease COVID-19, the US Federal Government, specifically the Department of Health and Human Services (HHS), declared a public health emergency on January 27, 2020. Under this circumstance, the Food and Drug Administration (FDA) may authorize expanded allowances for medical products that may be used to diagnose, treat, or prevent COVID-19. The Emergency Use Authorization (EUA) is a tool utilized by the FDA to grant temporary use authorizations for medical products that have not been cleared through the typical processes.
On February 4, 2020 the Secretary of the HHS determined, pursuant to Section 564(b)(1) of the Food, Drug & Cosmetics Act that there is a significant potential for a public health emergency that has potential to affect national security or the health and security of United States citizens. This is a necessary precursor to the FDA issuing EUAs. On this same date, the FDA issued its first EUA for the Center for Disease Control and Prevention’s Real-Time PCR Diagnostic Panel. EUAs have since been issued for more in vitro diagnostic (IVD) devices, personal protective equipment (PPE), and ventilators (and accessories). In addition, FDA has released guidance pertaining to EUA application requirements and enforcement of changes for the mentioned devices as well as remote monitoring devices, sterilizers, disinfectant devices, air purifiers, electronic thermometers, infusion pumps and accessories, ophthalmic assessment and monitoring devices, extracorporeal membrane oxygenation (ECMO), and cardiopulmonary bypass devices.
The following describes Emergency Use Authorizations and enforcement, the submission process, requirements, and duration for EUAs, and applicability for certain devices related to the current public health emergency.
Emergency Use Authorizations
In 2004, the Project BioShield Act was signed into law adding Section 564 to the Food, Drug, and Cosmetics Act (FD&C Act) allowing for the Emergency Use Authorization (EUA) of certain medical products. Section 564 was amended by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), the 21st Century Cures Act of 2016, and Public Law 115-92 in 2017. In order to sustain and strengthen national preparedness in the event of a public health, military, and domestic emergencies involving chemical, biological, radiological, and nuclear (CBRN) agents (including a infection disease threats such as a pandemic virus), the PAHPRA grants key legal authorities to the FDA. The PAHPRA clarifies and enhances the FDA’s authority to support the emergency preparedness and response and coordinate development and availability of medical countermeasures (MCMs). MCMs include drugs, biological products, and devices. With these provisions, Section 564 allows the HHS Commissioner to authorize emergency use of unapproved medical products or unapproved use of an approved medical product to diagnose, treat or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when there are no adequate, approved, or available alternatives. EUA candidate products include medical products and uses that are not approved, cleared, or licensed under sections 505, 501(k), and 515 of the FD&C Act or section 351 of the Public Health Service (PHS) Act.
PAHPRA includes language that gives provisions to the FDA for allowances outside of the EUA. Section 564A empowers the FDA to extend the expiration date of an eligible FDA-approved MCM stockpiled for use in a CBRN emergency, and to establish appropriate conditions relating to such extensions, such as appropriate storage, sampling, and labeling. 564A also permits FDA to waive otherwise-applicable current good manufacturing practice (CGMP) requirements to accommodate emergency response needs and permits the Centers for Disease Control and Prevention (CDC) to create and issue “emergency use instructions” concerning the FDA-approved conditions of use for eligible products. Furthermore it allows dispensing of MCMs during a CBRN emergency event without requiring an individual prescription for each recipient of the MCM or all of the information otherwise required or dispense by responders who may not otherwise be licensed to dispense, if permitted by state law in the state where dispensing occurs or if in accordance with an order issued by FDA. Lastly, Section 564B, also added by PAHPRA, permits government stakeholders to pre-position (stockpile) MCMs in anticipation of FDA approval or clearance, authorization of an investigational use, or issuance of an EUA. This enables these stakeholders to prepare for potential rapid deployment during a CBRN emergency.
Once the conditions have been met and a determination and declaration has been made by the HHS, the FDA may issue EUAs. The issuance may only occur after all four (4) statutory criteria have been met: 1) Serious or life-threatening disease or condition; 2) Evidence of effectiveness; 3) Risk-benefit analysis; 4) No alternatives.
- Serious or life-threatening disease or condition: COVID-19 has been determined to meet the “Serious or life-threating disease or condition” criteria and referred to in the public health emergency declaration by the HHS Secretary. Previous EUA declarations by the HHS include the Ebola and Zika viruses.
- Evidence of effectiveness: A determination of the evidence of effectiveness is performed by the FDA through the risk-benefit analysis. Medical products that may be considered for an EUA are those that “may be effective” to prevent, diagnose, or treat serious or life-threatening diseases or conditions that can be caused by the declared threat. The “may be effective” standard for EUAs provides for a lower level of evidence than the “effectiveness” standard the FDA uses for product approvals.
- Risk-benefit analysis: This determination and analysis are performed on a case-by-case basis. The FDA intends to look at and assess the totality, quality and quantity, of the available scientific evidence. This may include results of foreign and domestic clinical trials, in vivo efficacy data from animal models, and in vitro The product may be considered for an EUA if the Commissioner determines that the known and potential benefits of the product outweigh the known potential risks of the product.
- No alternatives: Finally, for the FDA to issue an EUA, there must be no approved, adequate, and available alternative to the candidate product for diagnosing, preventing or treating the disease or condition. Inadequate products are those products with contraindicating data for special circumstances or populations; dosage forms of an approved product is inappropriate for use in a special population; or if the agent is or may be resistant to approved and available alternative products. The available condition is determined in response to the emergency need and the supply of approved alternatives to meet the need. Recently released FDA enforcement guidance have shown that adequate and available products have been insufficient to meet the need of the emergency. Enforcement discretion and EUA information based on device assessment is addressed.
It needs to be stated clearly that Emergency Use Authorizations issued by the FDA are not clearances or approval for medical product use outside of the declared emergency. FDA will specify the effective date of an EUA issuance. The agency may revise or revoke an EUA if the circumstances justifying its issuance no longer exist, the criteria for its issuance are no longer met, or other circumstances make a revision or revocation appropriate to protect the public health or safety. Such circumstances may include: significant adverse inspectional findings, reports of adverse events (number or severity), product failure or ineffectiveness, a request from the sponsor to revoke the EUA, a change in the risk-benefit assessment, or a change in the approval status of the product may make an EUA unnecessary, or other circumstances determined by the FDA. Upon revocation of an EUA or its termination, an unapproved product or its labeling must be disposed.
Respirators, Surgical Masks, Decontamination:
Ventilators, ventilator connector tubing, ventilator accessories:
Infusion Pumps and accessories: