Editor’s note: This article has been updated August 2021 to reflect the current state of the COVID-19 vaccines in the FDA approval process.

Vaccination is the process of protecting a person from disease by making him or her immune. Researchers often do this by delivering a small piece of the organism that mimics the disease—called an antigen—to the person. That person’s immune system then makes antibodies to the organism, just like it would against any foreign substance. Although simple in concept, vaccine development takes time and money.

“Because vaccines are given to prevent disease and not treat it, they are usually administered to healthy people, so the standards for safety are higher than other drug classes,” said Dr. Thomas Boyce, pediatric infectious disease doctor at Marshfield Children’s and clinician researcher at Marshfield Clinic Research Institute. “In addition, there is often a fine balance in creating a vaccine that is strong enough to induce an immune response but not so strong as to cause side effects. Thus, vaccines are some of the most highly regulated pharmaceuticals.”

The development of a vaccine proceeds through several stages: exploration, clinical development, and regulatory review and approval. At each stage, there are continuous assessments of manufacturing and quality control.

Exploration: 3-7 years

The initial steps of vaccine development usually take place in a university research laboratory with funding by the federal government. This may include testing the investigational vaccine in small animals, such as mice. If the preliminary data appear promising, collaboration with a vaccine manufacturer may occur. This stage may take a few to several years, depending on the vaccine.

Clinical development: 7-9 years

Clinical development includes four stages of clinical trials:

• Phase I trials test the vaccine in a small number of healthy adults. These trials generally include less than 100 people, mainly assess safety and typically take one to two years.
• Phase II trials involve a larger number of people, usually 100-200 people. Researchers continue to assess safety, but they also find which dose works best. Phase II trials generally take at least two years.
• Phase III trials are large, placebo-controlled trials, often including tens of thousands of people. While researchers continue to look at safety, the primary goal is to determine how well the vaccine works, or efficacy. Phase III trials can take several years, often four or five.
• Phase IV trials are post-marketing trials. Researchers conduct these large studies after the vaccine approval to look for rare side effects and effectiveness in specific populations.  Marshfield Clinic Research Institute performs Phase IV safety monitoring for many vaccines, including COVID-19 vaccines.

Regulatory review and approval: 1-2 years

The vaccine manufacturer must apply to the Federal Drug Administration (FDA) for a biologics license application (BLA).  The FDA’s Center for Biologics Evaluation and Research (CBER) is responsible for licensing of the vaccine. The FDA requires laboratory testing for vaccine purity and consistency both before and after licensure. It inspects the manufacturing facility where the vaccine manufacturer produces the vaccine. The FDA also reviews all data from all clinical trials of the vaccine. This process typically takes 1-2 years.

“Vaccine development typically takes about 10-15 years, if all goes well. It costs hundreds of millions of dollars to develop a vaccine, and only about one in 15 vaccines that are entering Phase II trials ever becomes licensed,” Dr. Boyce said.

Vaccine development is a collaboration between academia, the government and the pharmaceutical industry. However, it is primarily pharmaceutical companies that incur the financial risk. We appreciate the ingenuity and perseverance of people who develop vaccines as vaccines are one of the best tools we have to prevent illness.

Process for COVID-19 vaccine

Although COVID-19 vaccines became available much faster than the typical timeline listed above, it is important to realize that they were studied just as thoroughly as any other vaccine.  Dr. Boyce explains the reason COVID-19 vaccines were available so quickly is because the vaccine companies did not wait to manufacture large quantities of vaccines until after they were approved.

“In some cases with government funding, they manufacture the vaccines while they are under review so they would be available much sooner,” he said.

Three COVID-19 vaccines are currently available under an emergency use authorization from the FDA.

“The timeline from discovery of the virus to development of available vaccines in about a year is remarkable. This was the result of unprecedented effort of scientists and investment by the government in funding the manufacturing of the vaccines in anticipation of their approval,” Dr. Boyce said.

A fully FDA approved product can be sold directly from a manufacturer to health care entities. All three COVID-19 vaccines Janssen (Johnson & Johnson), Pfizer and Moderna have met FDA approval standards for safety, effectiveness and manufacturing quality. Therefore, each submitted for full approval and are under priority review. FDA approval will allow direct sales and safety and effectiveness testing will continue after approval.

For more information about vaccines, talk to your health care provider.