Professionalism/FDA and the Emergency Use Authorization

The United States Food and Drug Administration (FDA) is responsible for "protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices." The global pandemic caused by SARS-COV-2 (COVID-19) occurring in the U.S. from early 2020 to present times presented scenarios that required the FDA to determine how to approve new medical products. The FDA needed to balance outside pressure, its public image, and its stated mission when making decisions regarding the Emergency Use Authorization (EUA). This casebook chapter will limit its scope to the specific decisions made during the COVID-19 pandemic.

Emergency Use Authorization, Defined

The FDA defines an Emergency Use Authorization (EUA) as a "mechanism to facilitate the availability of medical countermeasures... during public health emergencies." This provides a fast-track route to the public market for companies to be able to legally sell their products within the United States.

An EUA is a different route of approval than filing for FDA Approval. A company can choose between pursuing an EUA or regular FDA approval and different guidelines dictate each. While the research and development stages of the medical product is unchanged no matter what route is pursued, pursuing EUA allows for production to occur at the same time as testing , rather than after testing, the normal procedure. After testing, approval can be given and then distribution may occur.

It is important to note that filing for an EUA does not change the testing requirements that the FDA stipulates, simply the timeline of when certain production stages may occur. However, several important criteria must be met to lead to a successful EUA approval, including:

• No other medical alternatives exist
• Completed Phase 3 clinical trial
• All safety information, including follow-ups, submitted
• Also includes chemistry and manufacturing data

The FDA has previously used the EUA procedure to approve medical products related to the following:

• H1N1 Virus
• MERS-CoV
• Ebola virus
• Zika virus

Ethical Considerations for an EUA

There are several reasons that the use of EUAs could be considered ethical, such as:

• Expedience - An EUA protects the public health with getting products to market quickly

• Safety - The EUA does not compromise screening requirements

• Conditional - An EUA product must be continually safe, effective, and secure

The use of EUA's might also be considered unethical for the following reasons:

• Long-Term Effects - Expedited timescales could prevent the discovery of long-term effects, endangering the public health

• Rushed Timelines - Avoidable errors could occur during testing, production, or distribution that lead to public harm or delays

• Control - Medical products and opinions on them are difficult to control or redact once they are on the market or in public

The FDA and Pressure

The FDA experienced pressure from multiple sources during the Covid-19 pandemic. It felt political pressure from the Trump administration to authorize treatments and a vaccine before election day, and political pressure from other countries as they developed their own vaccine, since the US didn't want to be left behind or be reliant on a vaccine from another country. The FDA also felt pressure from the public to issue EUA's for treatments that could help patients suffering from severe Covid, as well as for a vaccine that could make everything go back to normal. Finally, there was likely some pressure from companies for the FDA to approve their drugs for commercial use.

The Trump administration in particular pressed the FDA to approve treatments and a vaccine as soon as possible. Trump wanted a vaccine out before election day, and called the FDA a “big, old, slow turtle” for not issuing an EUA for one faster. The FDA decided that for a vaccine to be approved, it would need two months of data first. This meant a vaccine would be unlikely to come out before election day, which Trump interpreted as a political move. Trump also pushed the FDA to issue an EUA for several experimental Covid treatments.

COVID-19-Specific EUAs

When deciding whether to issue an EUA for a experimental treatment, the FDA is in a tough situation. They have a duty to only authorize treatments that will be safe for public use, so they need good data to do so. But if they take too long to approve a treatment that could be helpful, the public will often accuse them of waiting too long without doing anything to help those suffering from Covid. There were many claims that the FDA was willing to keep people's lives in danger during the pandemic. If the FDA issues an early EUA for treatments without enough data, however, they will lose respect from the scientific community, and if they then have to later revoke that EUA, it will degrade public trust. This happened in at least two instances.

Hydroxychloroquine

Hydroxychloroquine, a drug typically used for treating malaria, became supported by many officials under Trump after two studies which seemed to show some effectiveness of Hydroxychloroquine at treating Covid-19. These studies were small, each with 100 or less patients, and in one of them, patients with the drug were given double the amount of steroids compared to the control group. The Trump Administration pressed the FDA to issue an EUA for the drug, and eventually the FDA did. Later rigorous studies, however, didn't find it to be effective at treating Covid patients, and after a study that attested the drug could cause severe cardiac arrest, the FDA revoked the EUA. This caused some officials to worry about the degradation of public trust in the FDA.

Convalescent Plasma

Convalescent Plasma was another treatment pushed by the Trump administration. The treatment involves taking the blood plasma full of antibodies from patients that had recovered from Covid-19, and donating it to sick patients to boost their immune system. The FDA approved the treatment while weren't any rigorous, well-controlled trials that showed strong evidence that it helped fight the virus, leading to more accusations of bowing the pressure. After later studies showed limited effectiveness, the FDA updated the EUA to only allow use of plasma with large concentrations of antibodies, which could further degrade public trust.

Outside Opinion on the FDA

Public Opinion and Reactions

The FDA has maintained public trust through its record of strict review policies for approval and authorization, and its experience in handling other viruses, like H1N1, Zika Virus, and the Ebola Virus. However, during the COVID-19 pandemic, public trust has eroded: The number of Americans somewhat or very likely to get a vaccine if it were available dropped between April 2020 and December 2020. This drop was consistent across all races and genders, and some attribute the decline in willingness to a lack of trust in the FDA’s vaccine approval process. As mentioned above, allegations of political interference also diminish public trust in the FDA. The fact that these allegations are even brought up is a signal of the FDA’s loss of trust.  These surveys were taken while vaccines were still in development, and David Altman, the president of the Kaiser Family Foundation, worries, “public skepticism about the FDA and the process of approving a vaccine is eroding public confidence even before a vaccine gets to the starting gate”.

Expert Opinion and Reactions

Experts have also weighed in on the use of the EUA to authorize vaccines, urging the FDA to exercise caution when issuing any EUAs. Eric Topol alludes to the EUA as a shortcut, warning “We are not in a high-trust mode, and the last thing you want to do is take a short cut and put everything at risk”. Arthur Caplan, president of the NYU medical school, encourages the FDA to “not put a COVID-19 vaccine on the U.S. market unless there is overwhelming evidence of safety and efficacy”. In a joint letter, the Infectious Diseases Society and the HIV Medicine Association urged, “While we believe that meeting the requirements for full approval is the surest route to maximum public trust and vaccine uptake, if a COVID-19 vaccine is made available via EUA, some specific actions may be necessary to shore up public confidence”.

Efforts to Restore Confidence

The FDA is working to restore public confidence, learning from past pandemics. A study conducted during the H1N1 pandemic showed that effective and clear communication is vital to trust in the FDA; use of words like ’experimental’ and ‘accelerated approval’ decreased confidence in a proposed H1N1 vaccine. If the FDA is to reinforce trust, its explanations of approval processes must be clear and straightforward. In an effort to increase public confidence in COVID-19 vaccines, the FDA announced new guidelines for the EUA process, including longer trials and more diverse trial pools. These guidelines increased confidence that the FDA was ensuring maximum safety of the vaccines and pushed hopeful vaccine approvals past election day, further mitigating worry over political pressure to issue an EUA. Also, the FDA held open meetings (comparable to town hall meetings) when discussing the use of EUAs for COVID-19, allowing the public to listen in on the discussions and fostering trust through transparency.

These efforts underscore the FDA’s professional goal: to ensure the safety of the public. To keep the confidence of the public, the FDA must maintain its strict standards and not succumb to pressures, even during health emergencies.