5 Key Facts to Know About FDA’s Emergency Use Authorization Process
How Emergency Use Authorization of Medical Products Helps Provide Relief During a COVID-19 Major Crisis
The current COVID-19 global pandemic continues to remain out of control. As we write this blog, over 60,000 new infections are being reported on a daily basis in the United States, with a cumulative total of over 4 million cases and over 150,000 deaths reported since the pandemic first began here.
It is a public health emergency of massive scale that has affected nearly all aspects of our life. It has caused enormous stress on our healthcare system and the economy as a whole. In a major crisis like this, it is good to know that the FDA has a special authority to quickly allow marketing of medical products that can help diagnose, mitigate or treat this highly infectious disease. Over the past 4 months or so, FDA has used this authority to authorize many different medical devices and diagnostics such as ventilators, RT-PCR tests, antibody tests, antigen tests, N95 respirators and decontamination systems, blood purification devise and remote patient monitoring systems.
In this blog, we discuss 5 key facts you must know about the Emergency Use Authorization (EUA) process if you are planning to get your medical product in the market to help during this emergency. This information can also help you plan ahead for future emergencies that will surely come our way sooner or later.
You can also watch a brief video about this process below.
1. Legal Basis and Process to Issue a EUA
The 2013 Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA) added or amended sections 564, 564A and 564B of the Food, Drugs and Cosmetics Act (FD&C Act), which provided new authorities to the FDA during a public health, military or domestic emergency involving chemical, biological, radiological and nuclear (CBRN) agents. Examples include the current COVID-19 pandemic, an act of bioterrorism, military conflicts, nuclear accidents or an environmental disaster.
Section 564, in particular, enables the FDA Commissioner to authorize the use of an unapproved medical product, or an unapproved use of an approved medical product during such emergencies. Note that this authorization is separate from the Investigational Drug Exemption, or Investigational Device Exemption including Compassionate Use. The trigger point is a declaration of a national emergency by the Secretary of Health and Human Services (HHS), also called an EUA declaration. This could happen if a real or potential emergency is considered imminent by the Department of Defense, Department of Homeland Security or Health and Human Services. The FDA Commissioner is then able to issue one or more Emergency Use Authorizations (EUA) to medical products that can provide relief during any emergency. Each EUA is unique and is issued on a case-by-case basis using certain criteria as discussed below.
2. Criteria for Issuing EUA for Medical Products
FDA uses 4 different criteria to determine if a medical product can be authorized for emergency use during the EUA declaration period:
Serious or Life-Threatening Disease or Condition:
o Does the CBRN agent involved in the EUA declaration cause a serious or life-threatening condition or disease? For example, the novel coronavirus SARS-CoV-2 is now proven to cause life-threatening condition and even death
Evidence of Effectiveness
o Is the medical product effective to prevent, diagnose, or treat serious life-threatening conditions or disease caused by the CBRN agent? For example, if there is evidence to show that a COVID-19 test has enough sensitivity and specificity for SARS-CoV-2, then FDA may issue EUA. Typically, EUA requires a “lower burden of proof” compared to the 510(k) clearance or PMA approval. This determination is made on a case-by-case basis after considering the risk-benefit balance.
Risk-Benefit Analysis
o Do the benefits exceed known and potential risks? For example, if a COVID-19 molecular or antigen test has only 80% sensitivity to detect SARS-CO-2, but it can provide rapid results in 15 minutes at point-of-care, it may still have a favorable risk-benefit balance.
No Alternatives
o Are there any other alternatives to the medical product under consideration for EUA? If the answer is yes, then FDA may not issue an EUA. There may be a situation where an approved product exists, but there is a severe supply shortage. Or there may be an approved product, but it may be contraindicated for a specific population particularly affected by the CBRN agent. For example, there are many approved ventilators in the market, but there was a very high demand and insufficient supply in the early phase of the COVID-19 pandemic. As a result, FDA granted EUAs to several ventilator models that could be produced by auto-manufacturers in partnership with a medical device manufacturer.
3. Steps to Getting an EUA
Getting an emergency use authorization for your medical product can be quick, but good planning is very helpful. Keep in mind, that the FDA is actually motivated to get the most effective product, with the most favorable risk-benefit balance, out in the market as quickly as possible to help provide relief during an emergency situation. Consider the fact that the FDA has rapidly authorized nearly 200 diagnostic tests in only a few months during the current COVID-19 pandemic.
The pre-EUA phase is an excellent opportunity to get early feedback from the FDA on your data package. For example, if you are thinking about a molecular diagnostic for at-home testing, similar to a pregnancy test, it would be highly beneficial to get feedback on your plans for a usability study. Note that this is a very high priority for the FDA given the current challenges with testing capacity. You can also take advantage of the weekly virtual Town Hall meetings where FDA is openly, and transparently, discussing their emerging thinking and offering real-time guidance. An emergency of this magnitude requires an all-hands-on-deck approach and you should definitely consider the FDA to be on your side if you have a potential solution to help solve this crisis.
The amount of data needed for a pre-EUA discussion with the FDA will depend on a variety of factors. Generally, the FDA recommends that you follow recommendations for submitting a pre-IND or device pre-submissions to the relevant medical product center. In the current COVID-19 situation, FDA has already provided different templates for COVID-19 diagnostic tests and enforcement discretion guidance for different medical devices. These are good resources for you to review as you prepare your data package for FDA feedback.
Once you are ready, you will need to formally submit a request for an EUA. Your data package needs to provide a summary including the intended use, target population, current approval status of the product, a review of alternatives, risk-benefit analysis and available capacity and/or near-term capacity expansion plans for the product. Sufficient details of safety and effectiveness data, as well as any relevant clinical and/or usability study data also needs to be provided. Depending on the situation, FDA may allow the use of benchtop studies, in-silico analysis, or limited clinical validation data for diagnostic devices. FDA may also allow partial data package to be submitted at first, with a plan to provide additional information as a follow up. In one case, an at-home collection kit was authorized with a plan for submitting additional use-error data on the first 1000 sample kits collected by patients.
The most important thing is to keep an open and transparent communication with the FDA. Having a track record of good Quality, Safety and Effectiveness helps.
4. Limited Duration
All Emergency Use Authorizations have a finite shelf life! When the HHS Secretary terminates the EUA declaration, all EUAs granted by the FDA are also terminated. There are other circumstances when a specific EUA may be terminated even before the EUA declaration is terminated. As an example, an unapproved use of an approved device authorized under an EUA may be terminated if the specific use is later approved by the FDA during the emergency. Another example is when the FDA determines that the safety and/or effectiveness of a particular product is no longer acceptable. As an example, FDA has revoked the EUA for several antibody tests when they failed to perform in independent validation studies. Similarly, they have removed several N95 respirators when they failed to pass the standardized testing by the National Institute for Occupational Safety and Health (NISOSH), the agency with oversight on PPE.
The key point here is that if you have invested significant resources in developing your product for an EUA, plan ahead to also submit for formal FDA approval or clearance.
5. EUA is not the same as approval or clearance
This point is very important – an Emergency Use Authorization is not a clearance (510k) or approval (PMA) for your medical device. In fact, FDA specifically prohibits you from making any such claims in your marketing materials and requires you to use specific labeling per the conditions of your EUA. During an emergency, many unscrupulous manufacturers make wild, unsubstantiated claims on their websites or other advertising. FDA has aggressively gone after then and issued several warning letters.
The best advice is to stick to required labeling and make plans to seek 510k clearance or PMA approval at the right time. In the meantime, continue to gather all the required data that can accelerate the review of your pre-market submission.
One good news is that all these EUA have a requirement to gather and report adverse events to the FDA during the authorized period. This can provide a lot of good information to address potential safety and effectiveness issues which can guide your data gathering activities for your pre-market submission.
In Conclusion
FDA has a legal authority to authorize medical products, which are not otherwise approved, or have a potential intended use that is not approved, during a public health, military or domestic emergency involving any of the chemical, biological, radiological and nuclear (CBRN) agents that can cause serious life-threatening conditions or disease. This authority allows the FDA to permit the use of medical products without having to go through the rigorous, often time-consuming, pre-market regulatory review process.
Medical device manufacturers can help provide relief during a national emergency, such as the current COIVD-19 crisis, by rapidly bringing their medical devices to market through the Emergency Use Authorization (EUA) pathway. Keep in mind that the emergency use authorization is valid only for a limited duration and is not a 510k clearance or PMA approval. It is a good idea to plan ahead and continue to gather relevant safety and effectiveness data to support a pre-market submission when the EUA is terminated.
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References
FDA Emergency Use Authorization Guidance – January 2020