By Richard Rupp and Bridget Hawkins
Editor’s note: This is the first of a two-part series.
Dear VaccineSmarts,
How do you know that vaccines are safe?
Jane
Bayou Vista
Dear Jane,
Our confidence in vaccine safety comes from the knowledge that vaccine development and manufacturing are heavily regulated and that even after licensure, vaccines are closely monitored for safety and effectiveness. The infrastructure surrounding vaccine safety is impressive.
In this country, all routinely recommended vaccines are licensed by the Food and Drug Administration. The route to licensure is highly regimented. Vaccine testing first occurs in several different kinds of animals. Researchers make sure that the vaccine does not cause illness or reproductive problems in the animals.
The FDA has a panel of vaccine experts that study the data from the animal studies and review the plan for human testing. The FDA only allows human testing to start once there is evidence that the vaccine may be effective and that the testing will be conducted as safely as reasonably possible. Of course, the FDA exercises an abundance of caution, as they cannot be entirely sure about the safety of a potential vaccine. People do not always react to vaccines the same way thatanimals do.
Tests in humans are called clinical trials. Clinical trials are conducted in phases. Vaccine testing can only progress from one phase to the next if its data demonstrate the vaccine is safe and well tolerated.
Phase 1 trials are also referred to as “first in human testing.” In Phase 1, the vaccine is typically given to 20 to 30 healthy adults. Only the healthiest of volunteers can participate in Phase 1 studies because they can best tolerate any adverse effects if some should occur. The volunteers are monitored closely for side effects. Monitoring usually includes extensive blood tests, physical examinations and frequent vital signs. The volunteers are observed for months to years following their last vaccination.
Phase 2 trials start once the FDA is comfortable that any common side effects from the vaccine are mild. Typically, 100 to 200 volunteers participate in Phase 2. The larger number of subjects allows for less common side effects to be detected. The design of Phase 2 trials usually produces evidence that the vaccine may be protective. Such evidence includes antibody levels or a decreased number of cases of illness. Monitoring does not usually require as much blood work and as many physical exams as Phase 1. Volunteers are usually observed for at least a year.
Ordinarily, thousands of volunteers participate in Phase 3 studies. The large number of volunteers allows for the detection of rare side effects. Monitoring of Phase 3 volunteers is not as close because there is a fair amount of safety information from the earlier phases. Volunteers may be observed for years to see if the vaccine loses effectiveness. A loss of effectiveness over time suggests the need for a booster dose of the vaccine.
The FDA also looks at the vaccine manufacturing process. The manufacturer must demonstrate the ability produce consistent batches of vaccine meeting high purity standards. The manufacturer must also demonstrate that the vaccine is stable during shipping and that the packaging ensures safe administration to patients.
The FDA only licenses vaccines once they are shown to be safe, effective and meet manufacturing standards. The whole process from bench research through licensure takes about 10 years and is costs around a billion dollars.