New Tools to Fight the Pandemic: FDA’S Emergency Use Authorizations for COVID-19 Devices
Among the bright spots amidst all the bad news lately are the frequent reports of how scientists and engineers have been mobilizing to fight the COVID-19 pandemic with new tests, new treatments and new preventative measures. On March 28, 2020, Abbott Labs announced FDA approval for a new COVID-19 test that can be run in a doctor’s office and return results within 15 minutes.
Ordinarily such innovations would be mired in the FDA regulatory approval process for months or even years before they could benefit patients. But now manufacturers can take advantage of an amendment to Section 564 of the Food, Drug and Cosmetic Act (FDCA) enacted in 2004, which establishes a faster path to market for medical products developed in response to a national emergency. This Emergency Use Authorization (EUA) program was utilized a handful of times prior to COVID-19, most notably in 2009 in response to the H1N1 swine flu pandemic. Now healthcare providers, medical device companies and other manufacturers seeking ways to address COVID-19 are asking how the program works and what it requires.
What does the EUA program do?
The EUA program permits the FDA Commissioner (under authority delegated by the Secretary of Health and Human Services, HHS Secretary) to authorize: a. the emergency use of approved medical products for purposes that have not been approved by FDA; or b. the emergency use of medical products that are unapproved for distribution in the U.S. market. Examples may include both entirely new innovations and products that are approved for distribution in other countries that have not yet received a PMA or 501(k) clearance here. It is important to note that receiving an EUA approval is not equivalent to gaining FDA’s blessing to circumvent its ordinary approval process. Rather, an EUA permits the distribution of covered devices only on a temporary basis, for the limited purpose of addressing an ongoing public health emergency. Manufacturers seeking to gain longer-term access to the market should begin working through the much more cumbersome processes applicable in the absence of an EUA.
What is required for an EUA to be issued?
Before FDA can issue an EUA, the HHS Secretary must first issue an “EUA declaration” finding that the action is justified because one of four circumstances exist: 1. a domestic emergency involving risk of attack with chemical, biological, radiological or nuclear (CBRN) agents; 2. a military emergency involving a risk of attack with CBRN agents; 3. a public health emergency with the potential to affect national security or the health and security of U.S. citizens abroad that involves CBRN agents or a disease or condition attributable to such agents; or 4. the identification of a material threat that is sufficient to affect national security or the health and security of U.S. citizens living abroad.
The HHS Secretary issued an EUA declaration for COVID-19 effective February 4, 2020 (the Declaration). The Declaration found that there is a public health emergency that has the significant potential to affect national security or the health and security of U.S. citizens living abroad involving the SARS-CoV-2 virus, which causes the COVID-19 illness.
Once the HHS Secretary issues an EUA declaration, FDA can issue an EUA for a particular medical product only upon finding that four statutory criteria have been met: 1. The CBRN agent cited in the declaration must be capable of causing a serious or life-threatening disease or condition; 2. FDA must find that the medical product “may be effective” either to prevent, diagnose or treat the disease or condition caused by the identified CBRN agent, or to mitigate a disease or condition caused by an FDA-regulated product that is used to diagnose, treat or prevent a disease or condition caused by the CBRN agent; 3. FDA must determine that the known and potential benefits of using the product to treat the disease or condition outweigh the known and potential risks; and 4. FDA must determine that there are no adequate, approved or available alternatives to treat the disease or condition. The “may be effective” standard for EUAs involves a lower level of evidence than the “effectiveness” standard for FDA approvals, and the risk/benefit analysis involves a review of the “totality” of current scientific evidence, including domestic and foreign clinical trials, in vivo and in vitro data, and other sources.
For general guidance on EUAs, see FDA, Emergency Use Authorization of Medical Products and Related Authorities: Guidance for Industry and Other Stakeholders (January 2017), (hereafter, EUA Guidance).
What EUAs has the FDA issued in response to COVID-19?
A single HHS EUA declaration may support issuance of multiple EUAs. To date, FDA has issued three categories of EUAs under the COVID-19 Declaration:
- Ventilators EUA (approving ventilators, ventilator accessories and connectors);
- Personal Protective Equipment (PPE) EUAs; and
- In Vitro Diagnostics EUAs.
The Ventilators EUA was issued March 24 and attaches an Appendix which, as of March 29, 2020, authorizes the use of three unapproved critical care ventilators and a ventilation expansion splitter from Prisma Health. Three PPE EUAs were issued on March 28 and 29, authorizing the use of a decontamination system, air purifying respirators, and disposable filtering facepiece respirators. And as of March 29, FDA has issued 20 separate EUAs for in vitro diagnostic tests for COVID-19.
What about 3D-printed devices?
The EUAs for COVID-19 do not address 3D printing. Although a number of 3D printing companies are seeking to distribute 3D-printed medical products in response to COVID-19, FDA has expressed general concerns about the safety and efficacy of 3D-printed, or “additive manufacturing” medical devices. For example, with respect to 3D-printed PPE, FDA notes that although 3D-printed PPE can provide a physical barrier to the environment, it is “unlikely to provide the same fluid barrier and air filtration protection as FDA-cleared surgical masks and N95 respirators.”
Notwithstanding these concerns, FDA entered into a Memorandum of Understanding (MoU) with the VA Innovation Ecosystem and the NIH 3D Print Exchange on March 25, 2020. This MoU is designed to facilitate collaboration and information sharing among the three agencies with respect to the development and procurement of 3D-printed medical products, standards for best practices in using such products, and related educational training materials. A high-level summary of this partnership can be found here. The website also includes information about FDA’s participation in America Makes, a private-public partnership that has created a website intended to track the specific needs of healthcare organizations during the COVID-19 pandemic and connect them with 3D printing companies with applicable capabilities.
How can a company get its products listed under an EUA?
The FDA strongly encourages medical products manufacturers to contact the appropriate FDA Center before submitting a request for an EUA if possible. Such early communications will facilitate a manufacturer’s understanding of the data, labeling and other information FDA would expect to receive in any EUA submission. General recommendations for EUA requests, as set forth in FDA’s EUA Guidance, include:
- A description of the product and its intended use
- A statement regarding the product’s FDA approval status
- A summary of the available scientific evidence regarding the product’s safety, effectiveness, risks and benefits for the emergency use
- A summary of any alternative approved products and their availability (or lack thereof)
- A discussion of the threats imposed by the CRBN agent involved
- Information regarding the chemistry, manufacturing and controls applicable at the sites of manufacture, and the current CGMP status of the manufacturing sites
- Information regarding the quantity of finished product available and any surge manufacturing capabilities
- Proposed labeling (instructions for use and “fact sheets”) to be supplied with the product for physicians and patients
- Testing and other data supporting any request to extend product expiration dates
- “Right of reference” authorization allowing the sponsoring manufacturer to rely on any relevant data submitted by other manufacturers in connection with other products
More specific guidelines regarding how to apply for EUAs under the three EUA categories currently authorized by FDA for COVID-19 are available here. These guidelines include FDA Center contact information, as well as templates and detailed requirements for EUA application format and content for each category of products involved.
What impact do EUAs have on healthcare providers?
FDA has consistently stated that it is not in the business of regulating the practice of medicine. For this reason, healthcare providers permissibly can—and often do—use medical devices for purposes that have not been approved or cleared by FDA. In some circumstances, such “off-label” uses even establish the standard of care within the medical community for treatment of a given disease or condition. Simply put, doctors don’t need FDA to issue EUAs in order to use medical devices in any way they see fit, within the exercise of their best medical judgment.
But such use can open healthcare providers up to potential malpractice liability. Using devices that are unapproved for distribution in the United States (as opposed to approved devices used off-label) can be particularly risky. But doctors who use or prescribe devices that are authorized for emergency use under an EUA may be immune from liability under the Public Readiness and Emergency Preparedness (PREP) Act, as is the case with COVID-19.
The HHS Secretary issued a declaration under the PREP Act providing liability immunity for activities related to medical countermeasures against COVID-19 effective February 4, 2020. Covered countermeasures include any “drug, biological product or device authorized for emergency use” in accordance with Section 564 of the FDCA. The individuals who can claim immunity under this declaration include not only the device manufacturers, but also licensed healthcare professionals. Healthcare providers who seek to combat COVID-19 using devices covered under an EUA are thus afforded immunity from potential lawsuits that they would not otherwise have.
What are the potential risks to the public?
EUAs reflect a balancing act: When it issues an EUA, the FDA has determined that a potential threat to public health is sufficiently serious and imminent to outweigh the need for collection of the more rigorous, time-consuming scientific evidence otherwise required to bring a medical device into the marketplace. But this bargain comes at a potential cost: Devices authorized under an EUA have not met the same safety and efficacy standards, and this opens the door to a greater degree of risk.
For example, the Ventilators EUA for COVID-19 explicitly contemplates potential authorization for the use of positive pressure breathing devices (CPAP machines) that have been modified for use as ventilators. But some experts believe these devices could contribute to spreading the disease by aerosolizing the virus. As National Public Radio recently reported, the use of CPAP machines to treat residents at the Life Care Center in Kirkland, Washington may have contributed to the devastating outbreak at that facility.
To be clear, FDA has not yet listed any CPAP machines among the devices authorized for distribution under the EUA. But the potential risks involved in using them highlights the trade-off we make when we use medical products for emergency purposes that have not been tested adequately.