Emergency Use Authorizations

In this ART podcast, Kevin Hennegan, Veristat’s Director of North American Regulatory Affairs, takes us through the many nuances key to the success of an Emergency Use Authorization application. 

Transcript

Speaker 1: 0:01

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Hello and welcome to the Art podcast, Advancing Revolutionary Therapies, a podcast series presented by the Centers for Excellence at Vata. My name is Kevin Hennigan, Director of North American Regulatory Affairs. Today I will be presenting an overview of the emergency use authorization program available through the US fda. This episode is part of season three of the ART podcast, where we will be discussing various topics pertaining to navigating the US regulatory environment, and I encourage you to continue to listen to subsequent episodes as we have explore a variety of topics and issues associated with interacting with the US fda. So what are EUAs? Emergency use authorizations or EUAs are a mechanism that allows the US FDA to facilitate the availability of medical countermeasures for chemical, biological, radiological, and nuclear agents or CBRN agents, including emerging infectious disease threats such as COVID 19 and pandemic influenza during times of national emergency. Products that receive EUA may be legally marketed and sold in the United States for the duration of the emergency or until authorization is revoked by fda. So when can these be issued? FDA may only issue EUAs when there has been a determination of an emergency involving C B R N agents by the US Secretary of Homeland Security, the Secretary of Defense, or the Secretary of Health and Human Services, and that circumstances exist justifying the emergency use of drugs, biologics, and or medical devices. For FDA to issue an EUA under these circumstances for primary criteria must be met. One, the threat agent must be capable of causing a serious or life-threatening illness. Two, there must be enough evidence of effectiveness to conclude that the product may be effective for its proposed. Use a lower threshold than the effectiveness standard required for full approval. Three. A risk benefit analysis must conclude that the known and potential benefits of the product outweigh the known and potential risks, including consideration of the risks posed by the threat agent. And four, there must be no adequate approved and available alternative to the candidate product. The standards for adequate and available are usually interpreted quite broadly. For example, a product may be considered unavailable if there aren't enough existing doses to meet the emergency need. A product may be inadequate if it has contraindications for particular subgroups that are at risk in the emergency. What is the application process for an eua? Well, prior to submitting an EUA application, FDA encourages sponsors to engage the agency in pre eua interactions to discuss the potential suitability of the product for EUA consideration. While this is not an absolute requirement, these meetings are vitally important. Emergency situations evolve rapidly. So discussions with the agency to help to keep you on the right track with respect to data requirements, trial designs, and even application format, ensuring a more expeditious FDA review and increasing the probability of success when a full EUA is submitted. Pre EUA meetings follow the same request process and timelines as other FDA meetings such as pre I N D or pre NDA meetings and are considered type B meetings with respect to PAD Purdue. For classifications, though they are usually treated separately from other submissions on file with fda. When a sponsor believes they have collected all of the data necessary to fulfill the EUA requirements, they can proceed with submitting their request for drug and biologic submissions. Submitting the application electronically in common technical document format or CTD format may help accelerate the FDA's review of the application. However, in an acknowledgement of the emergency conditions, FDA can also accept other formats, even paper submissions for EUA applications. So let's talk a moment now about the data requirements. The data required to support an EUA must be sufficient to fulfill the four primary criteria I mentioned a few minutes ago. In practice this often means a lower data threshold than is typically required for a full NDA or vla. This might include regulatory flexibility, for example, with respect to completion of full process validation or a significantly shorter duration of safety follow up at the time of UA application. The data threshold can and does vary from one public health emergency to another and even through the life cycle of a given public health emergency based on understandings of real and perceived risks. The COVID 19 pandemic is certainly an example of this, where we saw the drug hydroxychloroquine receive an EUA early in the pandemic on the basis of small preliminary clinical studies. Subsequent studies did not validate those early efficacy results and FDA revoked the eua. I think it is safe to say that at this point in the pandemic and I am recording this podcast in September of 2022, an EUA application would not be accepted by the agency without considerably more data than were provided for hydroxychloroquine. So while the detailed data requirements may vary, FDA does recommend that the following elements be included in any EUA application. One, a description of the product and its approval status that is whether the product is unapproved or approved, but for a different use than the eua two, Available safety and effectiveness data. Three. A discussion of the risks and benefits including a discussion of the risks of the threat agents that spurred the emergency. Four, chemistry, manufacturing and control information. Five, The quantity of available product and the production capabilities of the manufacturing site. And finally, proposed labeling information and fact sheets. According to FDA guidance. Sponsors with right of reference may refer to data previously submitted to FDA in a marketing application I n D or master file as part of their eua application. However, in our recent experience, FDA has objected to cross-referencing INDs and prefers that the data be submitted directly in the EUA application. This is particularly important if the cross reference data is not an E C T D format as evaluating non C T D data will significantly slow down the FDA's review. That said, cross references to master files and approved marketing applications do still appear to be fully acceptable to FDA again as long as they are in CTD format. So if you are successful in obtaining an EUA for your product, how can that be converted into full approvals? So I'll start by saying that in general, UAS remain in effect for the duration of the emergency that precipitated their issuance. When the emergency declaration is lifted, the EUAs are no longer in effect and the product can no longer be marketed or commercially distributed within the United States. In addition, FDA will continually monitor the state of emergency as it evolves and may revoke EUAs if the risk benefit profile changes or if conditions of the eua are not met. EUAs cannot be directly converted into full approvals. Sponsors must submit a full marketing application appropriate to the product type just as they would under normal conditions. Formally issuance of an EUA does not alter the data requirements necessary to support full product approval. But in a practical sense, I do not think it would be fair to say that an EUA had no influence on the full marketing application. Those impacts may be positive such as a larger sample size available for the safety database or negative such as a more challenging environment for conducting controlled clinical trials. So it is important to plan ahead and discuss the post eua clinical development plan with FDA during pre eua meetings and interactions. I will close there for today, but of course there are many more nuances and details that are important to the success of an EUA application. Verta has extensive experience in this field and can help you develop a detailed strategic plan tailored to your product that will increase your probability of success. If you have specific questions about your program, please reach out through the links available on the ris.website and we will be happy to assist now. Keep listening to the art podcast series as we explore more nuances of the US regulatory environment. We will be back and talking to you again soon. Thank you for listening.

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