Understanding Emergency Use Authorization (EUA)
By Veeranna Lolla
COVID-19 has spawned a new vocabulary that includes words like social distancing and zoom meetings. Given the impact of COVID-19 on our lives and our great desire for solutions, public interest in pandemics, mRNA, and vaccine development has been unprecedented.
One of the terms that became part of daily news briefings as drug developers drew closer to an effective vaccine was Emergency Use Authorization (EUA). This is a term we don’t often use, to include those of us who work in the pharmaceutical industry, thankfully, because it is indicative of a public health crisis.
But what exactly is EUA, when is it used, and how does the public health community, FDA, and drug developers authorize the emergency use of drugs or other medical products?
Brief History of Approving Emergency Use of Drugs
Although we do not often find EUA in breaking news stories, the idea of public health officials having a way to safely authorize the emergency use of drugs or medical products has been around for more than half a century. In the 1950s a morning sickness drug called Thalidomide was made available to the public in Europe only to discover, years later, that it caused widespread birth defects. This case is a key historical reference for regulators emphasizing the importance of having formal review processes for drug approvals.
During the mid-1970’s, concerns over a new strain of influenza in the United States, related to the Spanish Flu of 1918, raised fears of a potential pandemic. A first-ever national vaccine program was introduced in the United States, however, reports surfaced that the vaccine may be causing Guillian-Barre’ syndrome. The fact that the pandemic never materialized, only served to obscure any lessons that were to be learned.
It was not until the events of September 11, 2001, and the subsequent anthrax mail attacks, that the United States had the national will and motivation to develop a formal process for authorizing emergency use of drugs.
Origins of EUA
In 2004 EUAs were authorized in the United States by the Federal Food, Drug and Cosmetic Act under Section 564 and was subsequently amended in Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA). 1
According to the act, the EUA provides a framework to sustain and strengthen the United States’ preparedness for public health emergencies from infectious disease.2 Additionally, the law recognizes the key role of the Food and Drug Administration (FDA) in public health emergency preparedness and its responsibility in fostering the development and availability of drugs, vaccines, and devices for use in emergencies.
In the United States, new drug regulatory approvals are typically initiated by drug developers. However, EUA cases require that the Secretary of Health and Human Services (HHS) declare a public health emergency. When this occurs, HHS, the US Center for Disease Control, FDA, the Center for Biologics Evaluations and Research (CDER), other government agencies, ad hoc organizations, and industry can become organized to quickly find solutions for reducing public risks to the health emergency. And, of course, this happened in 2020.
EUA and COVID-19
On February 4, 2020, the Secretary of HHS declared a public health emergency for the novel SARS-CoV-2 virus which causes COVID-19 and its variants. Initially an EUA was deployed for medical devices used in the diagnosis of COVID-19, but more quickly followed including, testing kits, remdesevir, convalescent plasma, propofol, and bamlanivimad, all for the treatment of COVID-19. The fact that we didn’t even have test kits to detect COVID-19 at the beginning of this pandemic seems like a distant memory.
The most recent and highly celebrated EUAs were for vaccines developed by Pfizer-BioNTech and Moderna, authorized in December 2020, and Johnson and Johnson authorized in February 2021. Shortly before writing this, we learned that some patients receiving the J&J vaccine had serious adverse effects, administration of the vaccine was paused, and a review was done before the pause was lifted. I’ll address this more, later in the article. It is important to note that authorized under EUA does not mean approved. It means that emergency use of a drug is authorized when having met certain statutory criteria in that there are no adequate, approved, and available alternatives.
What is Required by FDA for EUA?
Ultimately, FDA must determine that the benefits of a drug outweigh the risks, both known and potential, before issuing an EUA.
FDA’s determination is made from the final or interim analysis of the phase 3 clinical trial based on data that proves pre-specified success criteria has been met for the study’s primary efficacy endpoint. Regarding patient safety, the FDA will review all safety data gathered from phase 1 and 2 studies and additional phase 3 data will be reported within two months of the start of the phase 3 clinical trial.
Like standard drug approval processes, FDA must confirm that manufacturing is being conducted in a way that ensures quality and consistency. The FDA’s determination will be based on an evaluation of the chemistry, manufacturing, and controls (CMC) information for the drug and will include batch records reviews, site visits, and the previous compliance history of the manufacturing facility to assess current good manufacturing practices (cGMP). Using a contract development and manufacturing organization (CDMO) does not relieve the drug developer seeking a EUA of the responsibility for compliance.3
At a predetermined time, set in consultation with FDA and when sufficient data is available during phase 3, an independent Data and Safety Monitoring Board (DSMB) will review all available data and inform the drug developer of the results. At this point, if the results are sufficient, the drug developer formally requests an EUA from the FDA.
Lessons Learned from COVID-19 EUA
As I write this, nearly 25% of the US population has been fully vaccinated. It is an amazing feat considering the virus was discovered a little more than a year ago and the lessons learned by the cooperation across government agencies, industry, healthcare institutions, academia, and the public are significant.4
However, as with any new drug, phase 4 data is important and will be gathered and reported to FDA. Phase 4, also referred to as post market surveillance, is designed to detect any rare or long-term adverse effects over a much larger patient population over a longer period. For vaccines with a public health protection outcome, like the COVID-19 pandemic, the long-term tracking is vital.
Coincidentally, the J&J vaccine was paused not long after vaccines were administered to patients on a recommendation by the US Center for Disease Control (CDC) and FDA due to the reporting of serious adverse effects. The CDC reconvened the Advisory Committee on Immunization Practices (ACIP) and FDA separately reviewed the data, and the pause was lifted--a great example of how the US regulatory oversight system works.
A comprehensive understanding of adverse effects and efficacy may not be truly understood for years after a pandemic or other public health issue. In the earlier example from the 1950s, birth defects caused by Thalidomide weren’t fully understood for a decade after its use in Europe. So, the full impact of the COVID-19 pandemic vaccines may not be known for years, and data will likely be gathered and studied for far longer.
Despite the challenges of the past year, FDA issuing Emergency Use Authorizations (EUA) remains a rarely used tool in the arsenal of the US and the Secretary of Health and Human Services to combat a public health crisis.
Over the past 50 years, the US had refined and improved its ability to safely authorize the use of drugs and medical devices for emergency use. But, like any unapproved drug product, it must undergo clinical trial, it must be manufactured safely and meet cGMP standards, and it must undergo rigorous review and approval by FDA.
- Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA) | FDA.
- The PAHPRA also includes threats involving chemical, biological, radiological, and nuclear agents.
- Emergency Use Authorization for Vaccines Explained | FDA
- One Year In: Vaccines | Harvard Medical School
Pharmaceutics International, Inc. (Pii) is a US-based contract development and manufacturing organization (CDMO) located in Hunt Valley, Maryland. The experienced scientists, engineers, and staff at Pii pride themselves on adroitly employing a phase appropriate method of drug development for the prudent use of their client’s resources as they solve challenging problems. In addition to offering end-to-end development services, Pii manufactures a variety of dosage forms to include complex parenteral drugs and has a wealth of analytical testing capabilities. Its Hunt Valley campus has four aseptic suites with lyophilization capabilities. Our talented professionals stand ready to help!
ABOUT THE AUTHOR
Veeranna Lolla, RAC
Head of Regulatory Affairs
Veeranna Lolla, is the Head of Regulatory Affairs at Pii and is also responsible for Change Control, Supplier Qualification, Product Complaints and Annual Product Reviews (APRs).
Mr. Lolla has over 25 years of experience in the pharmaceutical industry. He formerly served as Director of Regulatory Affairs at Strides Pharma USA. Prior to Strides, he held positions of increasing responsibilities at Endo Health Solutions and Sun Pharma USA, in the areas of CMC Regulatory Affairs, Technical Services, Manufacturing and Quality Compliance. He filed numerous ANDAs, amendments, supplemental ANDAs and NDAs for a variety of dosage forms, IR and ER Tablets, Capsules, Soft Gelatin Capsules, Sterile Products, Topical Formulations and Transdermal Patches. He has a proven track record in filing and winning approvals for first to file and first-time generics.
Mr. Lolla received his Masters in Pharmaceutical Sciences (Pharmaceutics) from Mangalore University, India. He received his RAC certification from the Regulatory Affairs Professional Society (RAPS).