Each person’s immune system works differently, so occasionally a person will not respond to a vaccine. Very rarely, a person may have a serious adverse reaction to a vaccine, such as an allergic reaction that causes hives or difficulty breathing. But serious reactions are reported so infrequently—about once every 100,000 vaccinations—that they can be difficult to detect and confirm. More commonly, people will experience temporary side effects, such as fever, soreness, or redness at the injection site. These side effects are, of course, preferable to getting the illness.
Most vaccines are designed to prevent illness and are given to people who are not sick. That is one reason that the bar of vaccine safety is set so high. To make vaccines as safe as possible, the Food and Drug Administration (FDA) requires extensive research and testing before allowing a vaccine to be licensed for general use.
The time between discovery of a disease agent and production of a widely available vaccine has been as long as 50 years. Today, with improved technology and research methods, the length of time from basic research to availability of a licensed vaccine can sometimes be reduced. If a vaccine is approved, FDA and other government agencies continue to monitor it for safety. The following are some of the key measures taken to ensure that vaccines are safe.
Lab and Animal Testing
Also known as preclinical testing, this testing is required before the vaccine can be given to people. Researchers test candidate vaccines in cell cultures and in animals such as mice, rabbits, guinea pigs, or monkeys. If the vaccine appears promising in these preclinical experiments, it may go on to be carefully tested in people.
Investigational New Drug Application
Before any vaccine candidate can be tested in people, its sponsors must submit an Investigational New Drug (IND) application to FDA. This application must explain how the vaccine works, describe how it is manufactured, present all preclinical safety data, and propose a plan for human testing. The IND must also demonstrate the vaccine has passed a series of tests for purity and safety.
Studies in Humans
Once researchers receive FDA approval to test their candidate vaccine in human volunteers, they begin trials cautiously, starting with a very small clinical trial. If all goes well, successively larger phases of testing will be conducted. Phase I studies enroll 20 or fewer people and primarily test for safety. Phase II studies involve 50 to several hundred people. Phase II studies continue to test for safety, as well as to determine the best dosage and to gather preliminary data on a vaccine’s effectiveness. A Phase III or efficacy study, designed to thoroughly test the candidate vaccine’s power to protect against illness, involves many thousands of volunteers.
Because Phase III trials are complex and costly, researchers have introduced the intermediary Phase IIb trial. A Phase IIb trial provides preliminary information about how well the vaccine will work and helps researchers decide whether to move it into a Phase III trial. Phase IIb trials enroll more volunteers than a Phase II trial but fewer than a Phase III trial. A candidate vaccine that tests well in a Phase IIb trial would still need to be tested in a Phase III trial.
The application to FDA for a license to market a vaccine is called a Biologics License Application (BLA). This application must provide the results of all relevant human studies, describe all manufacturing and testing methods, and show the results of safety and purity tests on batches of the vaccine intended for public use. A BLA must also demonstrate that the vaccine manufacturers comply with all government standards, including those for production facilities, personnel, equipment, packaging, and recordkeeping. At this stage, FDA also inspects the manufacturing facility.
The BLA is reviewed first by a team of FDA experts, then by an advisory committee made up of scientists, physicians, statisticians, and consumer representatives. The committee votes on whether or not to recommend that FDA approve the vaccine.
Once a vaccine is on the market, FDA continues to monitor its safety. FDA periodically inspects the manufacturing facility, and it tests samples of the vaccine for potency, safety, and purity for as long as the vaccine is made. The manufacturer must also safety test each batch, or lot, of the vaccine.
In addition, most licensed vaccines continue to be evaluated with very large studies that look at tens of thousands of people who have received the vaccine. These Phase IV studies try to pick up rare or delayed adverse reactions that might not have been apparent in the smaller studies that led to licensure.
Finally, FDA and the Centers for Disease Control and Prevention gather information on licensed vaccines through the Vaccine Adverse Events Reporting System (VAERS). Anyone—health care providers, patients, and parents—can report adverse vaccine reactions to VAERS. FDA reviews weekly VAERS reports for each lot of vaccine in use, searching for anything unusual.