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

By: Megan Donahue, MD, FAAP

Curious about how vaccines are made in the United States? By the time a vaccine reaches your child, it has gone through years of careful research, testing and review to make sure it's safe and effective.

Here are the steps involved to ensure vaccines help us stay healthy:

✅ Step 1

Scientists at universities and medical centers spend years studying diseases and the infections they cause. They do tests to figure out which active ingredients to use in the vaccine. For example, they look for the best antigen—this is the part that lets the immune system know how to fight the infection. (Learn about Vaccine Ingredients: Frequently Asked Questions.)

✅ Step 2

Scientists at drug companies also review this work. In some cases, they may decide to work with the researchers to produce a vaccine.

✅ Step 3

When the vaccine is ready to test 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 safe to test in people.

✅ Step 4

After the FDA approval, clinical trials begin. There are three phases in clinical trials. The results are often published in scientific journals.

• In 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 side effects or reactions. This phase usually takes one to two years to complete.
  
  
• Phase 2 clinical trials begin only if there are no safety concerns in Phase 1. Several hundred people of different ages, health conditions, and backgrounds are involved in this phase. Making sure participants have a diversity of backgrounds and physical conditions is important; everyone involved wants the vaccine to be effective for as many people as possible.
  

  Placebo testing in phase 2 clinical trials

  If the clinical trials are testing a new vaccine, a group of participants will receive a placebo. The placebo is usually saline or another safe substance. If there is a vaccine already available and the goal is to create a new one, the placebo group may be given the older vaccine. Either way, placebos are always part of the process for vaccine clinical trials. Scientists compare results among those who received the vaccine and those who received a placebo or older vaccine. They also track side effects. Phase 2 usually takes two years or longer.
  
  
  
• Phase 3 clinical trials include thousands of participants. Some get a placebo or an older version of the vaccine, if it already existed. Both groups are closely watched to see how their bodies' immune systems respond. Scientists also keep track of side effects and whether participants end up getting the disease later, if they are exposed to it. In this phase, scientists also investigate how the vaccine should be stored. Phase 3 lasts three to four years.
  
  

✅ Step 5

While the vaccine is going through human trials, the FDA looks into how it will be made. Manufacturers must provide information about their facilities and production plans. The FDA also asks manufacturers to develop a detailed plan to safety test each batch of the vaccine.

✅ Step 6

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

• its benefits are greater than any risks
  
  

✅ Step 7

If FDA licenses the vaccine, then companies can make it and market it. A team of physicians, chemists, statisticians, pharmacologists, toxicologists, microbiologists and other specialists reviews the information. Then, they provide a recommendation to the FDA.

The American Academy of Pediatrics reviews this data and makes science-based decisions on whether to include childhood immunizations on its recommended immunization schedule.

✅ Step 8

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

✅ Step 9 & beyond

The work of making sure the vaccine is safe does not stop when the vaccine is approved. The CDC, FDA and other agencies and groups continue to closely watch for safety issues, side effects or long-term complications. Here is a list of the groups that monitor 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 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 groups 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 look into possible safety issues for licensed vaccines.

• The Clinical Immunization Safety Assessment Project (CISA) does clinical vaccine safety research. It evaluates complex cases of possible 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 also supports ongoing research on vaccines and vaccine safety.
  

More information

• Vaccine Safety: Get the Facts

• Fact Checked: Childhood Vaccines Are Carefully Studied—Including with Placebos—to Ensure They're Safe and Effective (AAP.org)

  
  

The views expressed in this manuscript are those of the author(s) and do not necessarily reflect the official policy or position of the Defense Health Agency, the Department of Defense, nor any agencies under the U.S. Government.