How Vaccines Are Developed, Safety Tested & Approved: Step by Step

​By: Megan Donahue, MD, FAAP

Curious how vaccines are made and tested before they become available in the United States? By the time a vaccine reaches your child, it has gone through years of scientific testing and regulatory review. Here are the many steps involved to ensure vaccines can safely equip your child to resist dangerous infections:

✅ Step 1

Scientists at universities and medical centers come up with ideas for vaccines and spend years researching those ideas. They test different antigens—part of the virus or bacteria the vaccine is designed to protect against. The goal is to see which antigens can prompt the immune system to provide the right protection against that infection. This step often involves testing potential vaccines in animals to see if they are safe and effective.

These scientists are usually funded by government grants or private nonprofit foundations. Other scientists evaluate their work at conferences and in peer-reviewed journals.

✅ Step 2

Scientists at drug companies also review researchers' work. They may approach them about working together to produce a vaccine.

✅ Step 3

When the researchers and the company are ready to test their vaccine in humans, they ask the U.S. Food and Drug Administration (FDA) for permission to start clinical trials. The FDA looks over the research done so far. Then, it decides whether the vaccine is reasonably safe to test in people.

✅ Step 4

With FDA approval, clinical trials begin. During Phase 1 clinical trials, the vaccine is tested in a small number of healthy people. Scientists see if it generates a good immune response. They also look for any adverse reactions, or side effects. Phase 1 clinical trials usually take one to two years to complete.

✅ Step 5

If there are no safety concerns, Phase 2 clinical trials begin. In this phase, several hundred people from various ethnic groups and ages get the vaccine. Some of them are healthy; others have pre-existing health problems.

One group of participants receives a placebo (an inactive substance with no vaccine antigen in it). Scientists then compare results among those who did and did not receive the vaccine. They also track side effects. Phase 2 usually takes two years or longer.

✅ Step 6

In Phase 3 trials, thousands of participants receive the vaccine. Again, some get a placebo with inactive ingredients. Both groups are watched to see what kind of responses their bodies' immune systems produce. Scientists also keep track of side effects and whether the people ended up getting the disease later, when they were exposed to it. In this step, scientists also investigate how the vaccine should be stored.

Phase 3 lasts three to four years. The results of these clinical trials often are published in scientific journals for review by other scientists.

✅ Step 7

While the vaccine is going through human trials, the FDA looks into how the vaccine will be produced. Manufacturers must submit information about their facilities and plans for making the vaccine. The FDA also requires manufacturers to develop a detailed plan to safety test each future batch of vaccines.

✅ Step 8

Companies then ask FDA for permission to distribute the vaccine in the United States. The FDA licenses a vaccine only if it has been proven safe and effective, and if its benefits are greater than any risks.

✅ Step 9

If FDA licenses the vaccine, then companies can make and market the vaccine. The FDA team that decides which vaccines become licensed includes physicians, chemists, statisticians, pharmacologists, toxicologists, microbiologists and others.

Another set of scientists at the Centers for Disease Control and Prevention (CDC) also reviews the data at this point; they make recommendations on how the vaccine should be used and if it should be added to recommended immunization schedules.

✅ Step 10

The vaccine is manufactured, and Americans can begin receiving it.

✅ Step 11 & beyond

The safety monitoring isn't over when the vaccine is approved. The CDC, FDA and other agencies and groups closely watch for safety issues, side effects or long-term complications. Here is a list of those who are continuously monitoring vaccines:

• The CDC monitors diseases that are reported to health departments nationwide, including after a vaccine has been introduced. Certain health departments are also asked to monitor every person who receives a particular vaccine and to report regularly.

• Health care providers, patients or family members who believe that someone who got a vaccine had a significant negative side effect can file a report in the Vaccine Adverse Event Reporting System (VAERS) system.

• The Vaccine Safety DataLink (VSD) monitors the safety of vaccines and conducts studies about rare and serious side effects. It uses the electronic records from patients in health care organizations across the United States.
  

• The FDA's Post-licensure Rapid Immunization Safety Monitoring System (PRISM) uses a database of health insurance claims to identify and evaluate possible safety issues for licensed vaccines.

• The Clinical Immunization Safety Assessment Project (CISA) does clinical vaccine safety research. It evaluates complex cases of possible vaccine side effects in specific patients. CISA is a collaboration between CDC and a national network of vaccine safety experts from medical research centers.

• The FDA Biologics Effectiveness and Safety (BEST) System uses multiple data sources and rapid queries to detect or evaluate adverse events and to study specific safety questions.

• The Department of Defense, Department of Veterans Affairs, and the Indian Health Service monitor vaccine safety and do vaccine safety research.

• The National Institutes of Health and the Office of Infectious Disease and HIV/AIDS Policy also support ongoing research on vaccines and vaccine safety.