This article describes how the process works. It is general information and not medical advice. Talk with a doctor, nurse or pharmacist about vaccines for you or your family.
News about vaccines often mixes up several different steps: a trial result, an FDA decision, a recommendation from a health advisory group and an insurance rule. They are separate stages with different bodies responsible for them. Understanding the sequence makes headlines easier to interpret.
Before testing in people
Development begins in the laboratory. Researchers identify a target, such as a protein from a virus or bacterium, and design a candidate vaccine. They test it in cells and, in many cases, in animals to look for signs that it triggers an immune response and for early safety concerns. This is called the preclinical stage.
To move into human trials in the United States, the sponsor, usually a company or research institution, submits an Investigational New Drug application to the Food and Drug Administration. Vaccines are regulated by the FDA’s Center for Biologics Evaluation and Research. The application includes laboratory data, manufacturing information and the proposed trial plan, and the FDA can allow the trial to proceed or place it on hold.
The three phases of clinical trials
Human testing generally proceeds in stages:
- Phase 1. A small number of volunteers, often tens of people, receive the vaccine. The main goal is to assess safety and to find an appropriate dose.
- Phase 2. Hundreds of participants are enrolled, sometimes with varying doses or schedules. Researchers look more closely at the immune response and common side effects.
- Phase 3. Thousands, sometimes tens of thousands, of participants take part, typically randomly assigned to receive the vaccine or a comparison such as a placebo or another vaccine. These trials are designed to show whether the vaccine works to prevent disease, and to detect less common side effects.
Independent data safety monitoring boards often review trial results while the study is running and can stop a trial early if there are safety concerns or clear evidence of benefit. Participants give informed consent, and the trials are overseen by institutional review boards.
How the FDA decides
After successful trials, the manufacturer submits a Biologics License Application. It includes clinical data and detailed information on how the vaccine is made, tested and controlled for quality. FDA scientists review the evidence, and the agency inspects the manufacturing facilities. For new or complex products, the FDA often convenes its Vaccines and Related Biological Products Advisory Committee, a panel of outside experts, to discuss the data in a public meeting. The committee’s vote is advice, and the FDA makes the final decision.
If the agency finds the vaccine safe and effective for the intended use, it licenses it, sometimes called “approval.” The label specifies who it is approved for and how it should be used.
An Emergency Use Authorization is a different, faster pathway that the FDA can use during declared public health emergencies when certain criteria are met. It is not the same as full licensure, and the evidence standard and process differ.
Who decides who should get a vaccine?
Licensure answers whether a vaccine is safe and effective. A separate question is who should receive it and when. That falls to the Advisory Committee on Immunization Practices, or ACIP, which advises the Centers for Disease Control and Prevention. After the committee votes, the CDC director decides whether to adopt the recommendation, which is then published in the CDC’s immunization schedules.
Those recommendations matter in practice. Many insurance plans are required to cover recommended vaccines without cost sharing under the Affordable Care Act, and the federal Vaccines for Children program relies on them to decide which vaccines it provides to eligible children. The membership, procedures and recommendations of advisory bodies can change over time, so it is worth checking the CDC’s current schedule and any updates.
How is safety monitored after approval?
Even Phase 3 trials cannot detect extremely rare effects, so monitoring continues after a vaccine is in use:
- VAERS, the Vaccine Adverse Event Reporting System, is run jointly by the CDC and FDA. Anyone can report a health event after vaccination. Because it accepts unverified reports, it is designed to spot signals for investigation, and a report does not by itself show that a vaccine caused a problem.
- The Vaccine Safety Datalink, a collaboration between the CDC and health care organizations, uses electronic health records to study safety in large populations.
- FDA monitoring systems that analyze health data for safety signals.
- Manufacturer studies that the FDA can require after approval.
When a signal is confirmed, the agencies can change labeling, update recommendations or, rarely, withdraw a product. The federal Vaccine Injury Compensation Program, created in 1986, provides a no-fault system for compensating people who have certain vaccine-related injuries.
Reading vaccine news
A few questions help sort out claims:
- Which step is being described? A trial result, an FDA action, an advisory committee vote and an insurance decision are different events.
- Who is the source? Primary documents, such as the FDA’s approval letters and the CDC’s schedules, are public.
- Is a small number of reports being presented as proof of harm? Reports to a monitoring system need investigation, and correlation is not causation.
Because vaccine topics attract confident but unreliable claims, the steps in checking a viral claim before you share it are especially useful, as is knowing how to tell reporting from opinion. For personal decisions, a clinician who knows your history is the right source of advice.
Sources: U.S. Food and Drug Administration; Centers for Disease Control and Prevention; National Institutes of Health; Health Resources and Services Administration
