FDA Emergency Use Authorizations 101: COVID-19 Medical Devices

Everything You Need to Know About Emergency Use Authorizations for Medical Devices to Test and Diagnose COVID-19

In early February, the Secretary of HHS declared that the circumstances presented from the COVID-19 pandemic justify “the authorization of the emergency use of in vitro diagnostics for detection and/or diagnosis of the novel coronavirus (2019-nCoV).”  As such, in an effort to expedite the availability of these diagnostic tests, on February 29, 2020, the “FDA issued an immediately in effect guidance with policy specific to this public health emergency. This guidance was updated on March 16, 2020.”  Since then, the Agency has granted emergency use authorization (EUA) to 44 test kit manufacturers.

2017 FDA Guidance Document on EUAs

In January 2017, the FDA published a final guidance document regarding EUAs for medical products and related authorities.

What is an Emergency Use Authorization (EUA)?

In that guidance, FDA states that, in certain emergency situations and after a national emergency has been declared by HHS, the Agency is permitted “authorize the emergency use of an unapproved medical product or an unapproved use of an approved medical product.”  Furthermore, the Commissioner of the FDA may issue an EUA to allow the use of a medical product to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by a chemical, biological, radiological, or nuclear (CBRN) agent if there is not an adequate, approved, and available alternative.

An EUA essentially relaxes regulations during times of national public health emergency where the benefits of a product coming to market outweigh the risks of forgoing the full, formal, and lengthy approval process.  This does not, however, exempt Sponsors from ever obtaining formal FDA approval.  As soon as the national emergency is over, products marketed under an EUA must apply for appropriate FDA approval in order to remain on the market.

Pre-EUA Activities & Submissions

Sponsors are encouraged to engage the Agency as early as possible regarding its potential EUA products, as this facilitates “more complete EUA requests and enhances FDA’s ability to review and ultimately grant the EUA as appropriate.”  As we always advise our clients, more interactions with the Agency, the better.

FDA prioritizes both pre-EUA activities as well as formal EUA requests based on a number of factors, including, but not limited to:

• Progress on product development targets or milestones
• Competing FDA obligations or exigent circumstances (e.g., user fee deadlines, other Agency priorities)
• Whether there is a significant likelihood that the product would be retained in or added to government stockpiles if the product is authorized for use in an emergency.

In the guidance document, FDA notes that “the extent of, and timelines for, review of such submissions will be determined on a case-by-case basis and will depend on the nature of the submission (e.g., whether an IND or IDE for the product already is on file), the circumstances of the emergency, and the workload of the review staff.”  Furthermore, although there is no set timeframe for responding to pre-EUA activities and EUA requests, FDA recognizes the critical and timely nature of these requests and makes every effort to respond as quickly as possible.

Submitting an EUA Request

When submitting an EUA request to the FDA, Sponsors should include the following information:

1. Summary of Recommended Information and/or Data
2. Recommended Safety Information
3. Recommended Effectiveness Information
4. Discussion of Risks and Benefits

Summary of Recommended Information and/or Data

This should include “a well-organized summary of the available scientific evidence regarding the product's safety and effectiveness, risks (including an adverse event profile) and benefits, and any available, approved alternatives to the product.”  The exact type and amount of data necessary will vary based the nature of the declared emergency; furthermore, the Agency may see additional data and information on a case-by-case basis to ensure all criteria for issuance of an EUA have been fulfilled.

In general, any EUA request should include the following:

• Description of the product and its intended use(s)
• Description of the product’s FDA approval status
• The need for the product, including identification of any approved alternative product(s) and their availability and adequacy for the proposed use, and the unmet need(s) the EUA would address
• Available safety and effectiveness information for the product
• A discussion of risks and benefits, including available information concerning the threats posed by the CBRN agent(s)
• Information on chemistry (as applicable), manufacturing, and controls; a list of each site where the product, if authorized, is or would be manufactured, and the current CGMP status of the manufacturing site(s)
• Information about the quantity of finished product on hand and the surge capabilities of the manufacturing site(s)
• Information comparable to an FDA-approved package insert or instructions for use; drafts of the “Fact Sheets” to be furnished to health care professionals or authorized dispensers and recipients of the product, which typically are part of pre-EUA discussions (see section III.E.1 of this guidance); and a discussion of the feasibility of providing such information in an emergency
• If seeking an extension of a product’s labeled expiration date, any available information in support of such an extension
• Any right of reference, as applicable

Recommended Safety Information

The nature and volume of safety information that must be submitted with an EUA request will vary depending on whether the product is approved for another indication and, in the case of an unapproved product, the product's stage of development.

If a Sponsor is seeking to use an approved product for an unapproved use and the “new indication uses a similar dose, duration, route of administration, or mechanism of action (as appropriate given the nature of the product), and the intended patient population is similar, to that for which the product is approved, FDA recommends that the request for an EUA reference the approved application, including right of reference as applicable.”

However, if the new use poses a different risk to the patient population, FDA recommends that Sponsors submit information from relevant in virto studies, animal toxicology studies, and, if possible, human clinical data and experience.

If the product in question has not been previously approved, the EUA should include any available preclinical testing data, such as in vitro and animal toxicology data, as well as FDA human safety information from clinical trials and individual patient experience be provided, if available.

Recommended Effectiveness Information

Any available relevant scientific evidence regarding the following should be included in an EUA request:

• Product's mechanism(s) of action to diagnose, treat, or prevent the disease or condition underlying the request
• For drugs, preclinical testing data, such as in vitro evidence of the effect of the product in preventing or reducing the toxicity of the specified agent
• Data on activity or effectiveness in animals that would contribute to understanding potential effects in humans, including but not limited to any animal efficacy studies available for products being developed under the Animal Rule
• Evidence from human experience relevant to assessing activity, effectiveness, and dosing (e.g., in published case reports, uncontrolled trials, controlled trials, and any other relevant human use experience)
• For drugs, data to support the proposed dosage for the intended use (including pharmacokinetics and pharmacodynamics data, and for vaccines or antibody therapies, immunogenicity and/or achievement of protective levels of relevant parameters of immunity)
• For IVDs, device performance data to support the intended use such as analytical sensitivity and analytical specificity, and data from testing fresh, contrived, banked or archived specimens

Discussion of Risks and Benefits

This should include:

• Measures taken to mitigate risk or optimize benefit
• Limitations, uncertainty, and data gaps
• A description of circumstances, if any, under which the product should not be used (e.g., contraindications)
• To the extent known, information concerning the threats posed by the CBRN agent(s) (actually or potentially) involved, and anticipated response and operational considerations that may be relevant to an assessment of risks and benefits

Additional information on declaring and terminating an EUA, criteria for issuance, etc., can be found in FDA’s final guidance document.

When to Submit Your EUA?

Because time is of the essence for Sponsors seeking EUA from FDA, the Agency is allowing manufacturers to go market with their diagnostic before the EUA is submitted.  The only caveat is that the Sponsor must submit the formal EUA within a reasonable amount of time, which the Agency believes is within 15 days of the product entering the market.  However, while this will help make products available a little faster, we do not recommend taking this approach.

We recommend that Sponsors gather all the necessary data, prepare and submit the EUA application, and obtain authorization from FDA prior to going to market.  This is because, if you submit your data after taking your product to market and the Agency comes back and has issues with the information contained within the application, they may request that the device be removed from the market until the issues are resolved.  If you submit the information in advance the Sponsor can resolve any issues the FDA may find and then get on the market appropriately.

Although our recommended approach may appear less desirable in the short term, it is likely to be the most effective and efficient approach long term.  If you are in the process of preparing to submit an EUA, there is no doubt that you are looking to gather all the data and compile the submission as quickly as possible.  We can help you accomplish this goal.  Our experts have extensive experience in this arena and have a proven track record of helping clients achieve successful outcomes with FDA.

FDA Has Issued 44 EUAs for In Vitro Diagnostics and Counting

As of April 23, 2020, FDA has authorized 44 in vitro diagnostic medical devices for emergency use.  Furthermore, there have been ten EUAs for various types of personal protective equipment (PPE), 18 EUAs for high complexity molecular-based laboratory developed tests (LDTs), and 43 EUAs for ventilators and other medical devices.  While this is extraordinary progress, the number of EUAs is only going to continue to increase before the COVID-19 pandemic comes to an end.

What does the future look like for these devices?

In the short term, the fact that these products have obtained EUA status means that they can remain on the market as long as the national emergency declaration is in place.  Although no one knows how long that is going to be, we do know that the last time a national emergency was declared in the US was in 2009 when President Obama declared a national emergency due to the H1N1 flu.  This lasted just shy of a year.

In the longer term, when all of this is over and COVID-19 is a not so distant memory, the products that received EUA approval will be required to obtain formal FDA approval in order to remain on the market.  We can help with all of this.  From the preparation and submission of your EUA request to the required FDA submission, our experts have the knowledge and expertise to assist you throughout the entire process.  Interested in learning more? Contact us today to find out how we can help you obtain successful interactions with the FDA.