FDA Delays COVID Vaccine Review

Bureaucratic delays prevent Americans from receiving the COVID-19 vaccine


On December 1, the UK pharmaceutical regulatory agency, the Medicines and Healthcare products Regulatory Agency (MHRA), approved the Pfizer/BioNTech COVID-19 vaccine. Meanwhile, the US will wait on the FDA bureaucracy to reach a decision.

The British will be able to start receiving the vaccine within days. Their focus will be on protecting the frontline workers and the elderly; those in the highest risk groups. Those in the highest risk groups in the US, on the other hand, will be forced to wait.

On November 9th, Pfizer and BioNTech announced that their vaccine was over 90 percent effective. A press release is no substitute for the actual data from the study, and review of the data is necessary. They applied to the FDA for an Emergency Use Authorization (EUA) on November 30th.  An EUA allows the FDA to streamline the approval process in the case of an emergency, or if running a clinic trial is impossible.

The FDA released a notice in the Federal Register on Nov. 27, giving the public information about the EUA approval meeting. This provided the public with the opportunity to comment on the proposals being discussed, which is the normal process for federal agencies issuing regulatory changes. Finally, on December 10th, the FDA advisory committee will meet to discuss the EUA request. Upon reaching a recommendation, the FDA will choose whether or not to act upon it, which the FDA commissioner Stephen Hahn said in an interview would likely be within a few days.

According to Dr. Hahn, the FDA has been and will continue to review data and generate reports to prepare for the meeting during this time. In his interviews, Dr. Hahn’s description of the process implies that he believes that slow equals safe. But this is a false dichotomy. Rather than setting an arbitrary deadline for how long approvals should take to be complete, approvals should last until a rigorous analysis can be completed. How much additional data will we be able to gather by waiting a week longer than the UK?

The EUA means that this is an emergency. On average COVID-19 deaths amount to over 1,500 per day. For much of the year, excess deaths were even higher than COVID-19 deaths. Whether those deaths are undiagnosed COVID-19 deaths or deaths due to our response does not matter; they are a result of the virus and need to be considered when we are weighing the tradeoffs. We need to consider the risk of the vaccine and the risks of people contracting COVID-19 without the vaccine.

Unfortunately, the FDA has a long history of risk aversion when considering these tradeoffs. Former FDA Chair Scott Gottlieb detailed the culture of risk aversion at the FDA and its pitfalls. Vahid Montazerhodjat and Andrew Lo used Bayesian decision analysis to analyze the FDA approval stance. They also find that the FDA is too conservative, overweighing the risk of ineffective treatments and undervaluing the cost of rejecting effective treatments for severe diseases. This lengthens the process from discovery in the lab to use as treatment, which already sits at an average of over 15 years.

But this risk aversion and slow process is outdated in today’s rapidly advancing world. Technology is progressing at a rapid pace. It took researchers at Moderna just two days to design their vaccine in January, something unimaginable years ago. The rapid speed with which researchers are able to isolate a problem and design a solution tailored to it is only increasing as our technology improves. For example, just this week researchers released that they have solved the 50-year-old protein folding challenge, successfully cultured meat grown in a lab, and discovered a treatment to de-age and regenerate neurons.

Just 10 years ago it would have been impossible for so many people to seamlessly transition to working remotely. It should be no shock that science is seeing these improvements too.

Despite the rapid advances or science and technology, the FDA is still mired in an outdated regulatory process designed for the world of fax machines, not smartphones. The regulatory process is more suited for the pre-internet age, stifled by much slower data collection and the movement of information. We need nimble regulations that are able to keep up, rather than arcane and ritualized procedures.

Of course, you can’t shorten the time to conduct clinical safety and efficacy trials, but the UK allowed Pfizer to submit information on a rolling basis to shorten the approval process timeline. The FDA can do that to make it easier. The FDA could also end the requirement to fax or mail in hard copies of data.

The FDA also has a history of moving the goalposts, and requesting additional data from pharmaceutical developers, lengthening the approval process. After some time on the market, the Multiple Sclerosis drug Tysabri was found to increase the chance of progressive multifocal leukoencephalopathy and was voluntarily withdrawn from the market. Despite the FDA advisory committee recommending only a warning accompanying the package, the FDA required they create a risk map and limited the availability of the drug, which they didn’t require for Rituxan, which was in a similar situation.

Similarly, the FDA added requirements during the EUA process. In October, they announced a 2-month post injection review for side effects for 50 percent of participants. This forced Pfizer to wait an additional month to apply in order to meet the requirement. Eric Topol worked to convince the FDA to add this requirement to lengthen the process. The FDA’s decision was called “bureaucratic jujitsu” by a supporter. I’d call it bureaucratic obstruction which cost the lives of thousands of people forced to wait for the vaccine. Meanwhile patients in the UK are able to receive that vaccine.

The UK approval should inspire us to enact a reform that is far overdue and is a simple alternative that still keeps the protections of a regulatory agency but will allow for some speed. We should have reciprocity agreements with regulators in other countries. This would allow any drug approved for use in another country to be used by American patients. Some countries, like Australia and New Zealand, already take FDA approval into consideration during their approval process.

The U.S. government can limit reciprocity to countries that have a proven track record of approving safe and effective drugs. This would include countries in the European Union, Canada, Japan, South Korea, and Australia. This reciprocity would reduce delay and limit wasting time and effort applying to multiple regulatory bodies. Comparing the approved drugs in the UK and the US, researchers have found no significant difference in the safety between the countries, suggesting that MHRA approval is no less safe than FDA approval.

Ensuring that the COVID-19 vaccine is safe and effective is important, no one is arguing that. The question is how long a process is necessary, considering the continuing death toll. While the FDA abides by their bureaucratic process, the MHRA has acted quickly and approved the Pfizer vaccine, allowing people in the UK to begin to be vaccinated.

The FDA approval process, even in their Emergency Use Authorization, is a long process, taking time and costing us lives.
