Development is only a part of the phases; once the development process is near complete, it goes to the U.S. Food and Drug Administration’s (FDA’s) Center for Biologics Evaluation and Research (CBER). This department is solely responsible for regulating vaccines in the United States. The department has its own process, which also includes several steps and sometimes steps within steps.
The first part is an investigation on the application of the new drug from the department completed pre-licensure vaccine clinical trials. The third step is a Biologics License Application (BLA), and the fourth step is when an inspection of the manufacturing facility. A fifth step is when the department presents its findings to the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) department. The final step is the usability testing of product labeling.
Once the vaccine is approved, it remains with the FDA as they need to continue to oversee the production. Part of this is because it’s up to them to ensure that everything follows ethical standards and is 100% safe for the public. However, the monitoring process isn’t as easy as you think because of the steps associated with the process.
There are various moments of inspection that include all the parts of the vaccine, including the facility. In fact, these inspections don’t end until the manufacturer no longer holds a license for that product. The manufacturer of the product also needs to periodically test and give the FDA reports that discuss the testing, safety, and purity of the vaccine.
Before Anything Scientists Need To Understand The Infection
You’ve received a quick rundown of the whole process for developing and accepting a vaccine, but there is one crucial step that happens before any scientists start even to mix a vaccine – research. Yes, research is completed through the whole process, but it’s the primary process at the beginning. It comes before scientists even start thinking about how to develop the vaccine.
Sometimes this part of the process is included in the exploratory stage, and other facilities leave it by itself. The purpose is to give themselves a direction; scientists need to understand the structure of the infection. They need to know as much as possible about it from where it originated to its symptoms. This part is incredibly important because, without it, scientists can’t mimic the infection to develop the vaccine.
If the facility conducts its basic research before the exploratory stage, they already have an idea of where they’re going with the vaccine. This stage usually lasts between two to four years and includes both governmental and academic scientists. It’s a federally funded stage, so if more money is needed, scientists will write up a proposal to receive more funding.
The point of this stage is to identify any synthetic or natural antigens that can help prevent the disease. Antigens include weakened bacteria, viruses, toxins, or other pathogens. It can also include virus-like particles.
Preclinical studies are a huge part of the preclinical stage. These are studies that are conducted before humans, whether it’s on animals or through another means. For instance, cell-culture systems or tissue-culture systems are used during this phase, along with animal testing. If animal testing is involved, there is a specific set of guidelines to follow on the monkeys or mice.
During the studies, scientists are looking at the immune response, safety, and many other factors. Preclinical testing gives scientists an idea of how humans will react to a vaccine. Results often indicated how the vaccine should change or what will make it safer.
There is a lot of back and forth for the team of scientists working on a specific vaccine during the preclinical stage. At the end of this stage, their main goal is to have the most effective vaccine possible, as this makes the rest of the process easier. There are several challenges that scientists face when it comes to this stage, from how to conduct the tests to measuring effectiveness.
The preclinical stage will last a couple of years, but some only last about a year. The length of time depends on several factors, from the number of team members to funding. It also depends on how many and what type of testing the scientists focus on.
Not all of the developmental phases happen one at the time. There are a few phases that are happening around the same time because different people work on them. On top of this, it helps ensure the vaccine reaches production sooner instead of 10 years down the road.
The IND application phase is one that occurs during other stages. It involves a sponsor, usually a private company, that will submit an application for an Investigational New Drug (IND) to the U.S. Food and Drug Administration. In this application, testing and manufacturing processes are discussed along with any type of reports from the labs.
There are hundreds of vaccines that scientists are working on at once. In fact, it probably reaches closer or into the thousands. All of these vaccines need to go through the FDA, which means they have to allow themselves time to review each application and vaccine carefully. Therefore, the length of time it takes for the FDA to approve an application is 30 days.
When the application reaches the FDA, they have a review board that takes a look at it. They note everything on the form and discuss each part. They ensure that both parties understand everything before approving. Once the application is approved, the vaccine moves on to further testing.
Human Subjects Get Involved After Approval From The FDA
IND application approval is usually a pretty exciting yet anxious time for scientists. Not only does it allow them to continue working on the vaccine, but it gives them peace of mind that everyone is going in the right direction. Scientists view the FDA as another set of eyes to ensure the safety of the vaccine.
The approval also means that scientists can start looking for human candidates to test the vaccine. To do this, they need to find people who are physically healthy or at least haven’t had the disease before. The plan is to infect humans with the virus so they can give scientists more information.
The first phase of the vaccine trials focuses on a small group of adults. They usually focus on a group of 20 to 80 people, who are called subjects. Even if the vaccine is meant for children, the first group of subjects is adults. Once the first group is completed, the scientists would look for a lower age group. This process continues until they reach their target age group.
Trials in phase I are non-blinded, which means subjects usually know if they are in the placebo group or vaccine group. The goal is to safely vaccinate the subjects so researchers can understand how they react to it. All people are carefully monitored and controlled.
In the second phase, scientists go from up to 80 subjects to several hundred. It’s also during this phase where they’ll look at people who may have some underlying health problems, so they learn of any risks with the disease and vaccine. The subjects in this phase don’t know if they are in the placebo group or received the vaccine. The trials are all randomized but also controlled.
Other than safety, other goals of phase II include immunogenicity, schedule of immunizations, proposed doses, and method of delivery. Once phase II is proven successful, which can take up to several months, the scientists move on to the next step.
A successful phase II subject can move on to phase III as long as they didn’t have complications. This phase also has new people because scientists want to test thousands of people; in fact, it’s usually over 10,000 people. They often also look out of their local area and ask in various states or cities. Like the other phases, some subjects are tested with the placebo while other people receive the vaccine. But, there is usually another group that will receive a different vaccine, meaning for another disease that’s already tested thoroughly.
The goal of phase III is to focus on safety and rare side effects. Scientists might notice rare side effects in phase II, but it’ll become more apparent in this phase. The reason why this happens is some side effects occur in 1 of every 10,000 people, so the rare effects don’t usually show until this phase.
One of the main focuses on phase III is the efficacy of the vaccine. There are three factors that this includes. The first is, does the vaccine prevent disease? The second factor is, does the vaccine prevent infection with the pathogen? A third common factor is if the vaccine leads to production or any other types of immune responses.
Once all of these questions are answered, the scientists ensure it’s all correct and then send it all for approval and licensure. During all three phases, the FDA is heavily involved and they become more involved once the scientists stamp their consent and for further approval. It’s important to note that scientists don’t send their subjects home without post-trial discussion and a complete exit procedure. What happens with the subjects varies, but there is sometimes forms of counseling and check-ins so the scientists can ensure that all the participants remain healthy and don’t have any lingering effects months later.
After Phase III The Approval And Licensure Phase Begins
Once the scientists are confident that their three phases are complete, they will focus on finishing up any reports and then send these along with any other paperwork and requirements to the FDA. This is when the Biologics License Application comes into consideration, and the FDA starts the other part of their process to ensure that everything is holding firm, guidelines are met, the vaccine does what it’s supposed to do, and safety is achieved.
The FDA inspects everything from the vaccine to the factory and laboratory that developed it. This approval is necessary as once the FDA approves the factory and lab, the scientists can start focusing on developing more of the vaccine for production. In other words, nothing more can be done until the vaccine is ready for the labeling process.
The Licensure Procedure Takes A Bit More Time After Approval
A big part of the licensure procedure is to monitor the production of the vaccine. Therefore, the FDA needs to approve the application and the lab so the scientists can continue working on the vaccine for output. Throughout this process, the FDA remains heavily involved, and they will stop at the facility more than once to ensure that everything is up to code, up to date, and running smoothly. The main goal for all parties is to ensure the safety and purity of the vaccine for production. Scientists work closely with the FDA as they want the best vaccine to head to the hospitals and clinics.
Many tests continue to happen during the phase, and the FDA is aware of all of them. The analyses focus on the vaccine’s purity, potency, and safety. In fact, the FDA can run their own tests along with the scientists without permission from the scientists. This is often considered a “double-check” phase or a second pair of eyes to ensure that everything is as perfect as possible.
You didn’t think that the vaccine was ready for shipping once the FDA approved the application and gave the licensing, did you? There are further monitoring and trials that come after the approval process. While they don’t last as long as the previous three tests, phase IV still takes a bit of time. However, it’s also an optional phase, so when a vaccine is meant to happen quickly, like with the current crisis, it might not happen. But, most scientists continue with phase IV to ensure that everything is safe and continues to run smoothly.
Phase IV trials focus on the drug companies that might want to conduct their tests once they receive the vaccine. When they do these studies, they work with the manufacturer to ensure efficacy and safety. One of the benefits of these studies is that they often lead to other potential uses. Sometimes this phase will also show that the vaccine can become more robust with a couple of changes, which brings the scientists back to the earlier steps and approval. However, this is all part of the job.
Once everything is approved, and all phases are complete to the point they have to be, the vaccine is sent to hospitals and clinics so the public can receive it. But, this doesn’t mean that the process is completely over. It means that now the CDC, FDA, and the scientists continue their reporting of the vaccine with the help of hospitals, clinics, and other experts. In 1990, the FDA and the CDC established a system that everyone uses called The Vaccine Adverse Event Reporting System (VAERS).
According to the CDC, this system is used to “detect possible signals of adverse events associated with vaccines.” In general, VAERS receives about 30,000 cases a year, with 10% to 15% described as severe medical cases that needed hospitalization. Other events that happened that are reported include life-threatening illness, death, or disability. It’s important to note that anyone can report to VAERS as its voluntary based, which means teachers and parents can also use it.
The Vaccine Safety Datalink Is Another After Production Process
In 1990, the CDC established a system known as the Vaccine Safety Datalink. This is a collection of linked databases that contain information from various large medical groups. The information that the datalink shows include what populations are more likely to get the vaccine. It allows the manufacturer, along with any other researchers the information they need to monitor the progress of the vaccine. However, they need to request approval from the CDC before they can access the datalink.
The datalink is still in the early stages, which means many changes continue to happen within it. For instance, it doesn’t have any information for unvaccinated children. It’s also known as data that is difficult to control and evaluate, which leads many scientists to find different ways to monitor the vaccine.
For a researcher, the work on any vaccine is never truly over. Even when it’s available for the population, they continue to do their research, monitor, and look at any necessary changes. They are also continuously looking at developing other vaccines that are an arm of their current strain because colds, cases of flu, and other diseases change over time, and this means the vaccine needs to change with them.
Developing and approving vaccines is a long process that usually takes years, so if a vaccine comes out within a matter of months, you need to thank hard-working researchers, experts, and the advancement in technology.
“Vaccine Testing and the Approval Process.” Centers For Disease Control and Prevention.
“Vaccine Product Approval Process” U.S. Food and Drug Administration. January 2018.
“How Long Will It Take to Develop a Vaccine for Coronavirus?” Shawn Radcliffe, Healthline. January 2020.
“HOW ARE NEW VACCINES DEVELOPED?.” Gary Finnegan, Vaccines Today. September 2012.
“Vaccine Development, Testing, and Regulation.” History of Vaccines. January 2020.