Exploring the steps to developing a vaccine

The global race to produce a
coronavirus cure

Four US drug companies are in the late-stages of trials on a possible coronavirus vaccine. This week, Johnson & Johnson announced that it is the latest developer to begin the final clinical trial stage. While they are behind their competitor’s (Moderna, Pfizer, and AstraZeneca), the Johnson & Johnson trial will be the largest, enrolling 60,000 participants. We connected with Dr. Maura Falli, a graduate of Albany College of Pharmacy and Health Sciences, on a recent HeartTalk episode, presented by Capital Cardiology Associates. Dr. Falli has an interest in research, academia, and critical care. She explained the timetable of drug development.

Vaccine companies started working on the genetic sequence of the coronavirus in January. This was before the virus reached the United States. The goal was to begin sharing scientific information on a new disease spreading in China and other parts of the world. Dr. Falli outlined what these discussions would most likely include. Researchers would “first begin by identifying the need,” she began. The next step would be to develop a few potential testing options, consider conducting trials first in animals, and then in humans. Finally, developers must submit various applications to the FDA along the way to gain approval to market these products. It wasn’t until early March that President Trump took the first step when he met with top drug manufacturers’ executives to discuss developing an American vaccine.

The timeline for developing a coronavirus vaccine has been a constant newsmaker this year. The current record for developing a vaccine is four years for the mumps vaccine. The process of bringing a vaccine to market typically takes about ten years. Dr. Anthony Fauci predicted “a year to a year and a half” for a COVID vaccine, even with an accelerated timetable. The goal of the Department of Health and Human Services (HHS) is to deliver “300 million doses of a safe, effective vaccine for COVID-19 by January 2021” as part of Operation Warp Speed (OWS). OWS is a never-before partnership of several federal agencies (including the CDC, FDA, National Institutes of Health (NIH) and Department of Veterans Affairs) coordinating with the Department of Defense for the rapid production of a COVID vaccine.

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Dr. Falli detailed why it traditionally takes years to produce a vaccine and how bringing a cure to market on a rapid timeline would be a massive win. “The stages are primarily in place to make sure that the vaccine is both safe and effective. The first step is to conduct extensive research, break down the virus’s genetic sequence, identifying the viable targets. Next, we develop the vaccine itself.” Over 100 vaccine candidates are currently under development; 14 promising candidates were narrowed down to 7, which were allowed to proceed to early-stage clinical trials. In this phase, scientists test on lab animals. If the vaccine passes those tests, the team moves to human clinical trials, broken into three phases. Dr. Falli elaborated, “Phase one is where we are screening for safety. This is typically done in a small group of patients. In this phase, we ensure that there are no safety issues or dangers with the vaccine itself. This is typically between 20-80 patients, a smaller evaluation group. Phase two is where we are evaluating efficacy. We are testing the vaccine in a small group of people who might be at risk of infection. You could also look at it as a small group of people who share a group of similar characteristics like age or gender, like the population that the vaccine is aimed at. In this phase, we are primarily determining that the vaccine works for the purpose that it is intended. Typically our phase two trials are larger than our phase one trials. Phase three is the final confirmation for safety and efficacy. Here were are testing a large group of people and monitoring for side effects. Phase three is larger than the other trial groups, as we build up in size.”

And what happens if a vaccine clears phase three? There is another lengthy analysis of the results, Dr. Falli shared. “After we are confident that the vaccine works and that it is safe, the next step is approval for mass production in general use. There actually is a phase four clinical trial that happens after the vaccine goes to market. This is known as post-marketing surveillance, continued monitoring of the drug after it has been widely released. Once we have the general population, millions of people, using the vaccine, we may notice some observations that did not occur in our smaller clinical trials. After we use the vaccine more globally or broadly, we can see these observations and report them to ensure continued safety and monitoring of the product after it is released.” Considering all of the steps and phases involved in vaccine development, it is obvious how ten years can pass from start to finish.

Not all drugs or vaccines see the finish line. According to a 2018 study from the MIT Sloan School of Management, nearly 33.4 percent of vaccines for infectious diseases in clinical trials eventually win approval from the FDA. The primary reason for failure is cost. Dr. Falli noted the astronomical amount of funding needed to bring a drug to market. “The median cost reported in a study on drug development quoted a price of $985 million, but it can be up to $2.6 billion depending on the nature or duration of the study.” Congress has appropriated about $10 billion to help companies with data analysis and development in the COVID vaccine. The idea behind government funding is to make a vaccine or treatment that is affordable for the American people. Public funding of research is also a new level of involvement in a process that is usually reserved for private companies. Incentivizing companies to produce doses of vaccines removes the burden of financial risk that is the largest barrier to success — a place known as the “valley of death” in drug research. This is the point where a lack of funding prevents research or discovery from clearing clinical trials in over 65% of vaccine progress.

The United States is one of several nations developing vaccine candidates. The World Health Organization is working with scientists and health partners in over 90 countries to guarantee rapid, fair, and equitable access to COVID-19 vaccines worldwide. The goal is to deliver two billion doses of safe, effective vaccines by the end of 2021. Currently, experimental versions in China and Russia have been reported to have reached the Phase 3 trial stage. These vaccines differ in how they attack coronavirus. The consensus in the scientific and medical communities is that there will be multiple vaccines for COVID. “It’s difficult to say at this time what the differences will be because so many of the vaccines are in the early stages of development,” added Dr. Falli. Ultimately, the best outcome is to have several vaccines produced to meet global needs across various age groups or demographics. “Until we have a vaccine, social distancing, wearing a mask, and frequent handwashing continues to be the most significant steps we can take to protect ourselves from the virus,” concluded Dr. Falli.

Written by Michael Arce, host of HeartTalk, presented by Capital Cardiology Associates