CDC ensures the safety of vaccines by:

  • Conducting vaccine safety research, done by the nation’s leading vaccine safety experts.
  • Assessing what could be the cause of an adverse event and identifying any potential risk factors.
  • Searching for adverse events following immunization (AEFIs) in multiple ways, mainly using three safety surveillance systems which each provide different insight into the vaccine use in the US population.

CDC’s Immunization Safety Office conducts 3 primary vaccine safety activities:

  • The Vaccine Safety Datalink (VSD)–a collaboration between CDC and several healthcare organizations which uses de-identified health records to monitor and evaluate adverse events following vaccination.

Vaccine safety monitoring continues to become more important with the development and use of new vaccines, expanded vaccine recommendations, and new global immunization initiatives. Reporting systems and vaccine safety activities, such as VAERS, VSD, and CISA, will continue to be used to monitor and study adverse events, so vaccines can continue to be held to very high standards of safety.

Read more about vaccine safety and monitoring at the CDC's Ensuring Vaccine Safety setion.


Monitoring Vaccine Safety: Pre-Licensure

Before vaccines are licensed by the FDA, they are tested extensively in the laboratory and with human subjects to ensure their safety. First, researchers use computers to predict how the vaccine will interact with the human immune system. Then researchers test the vaccine on animals including mice, guinea pigs, rabbits, and monkeys.

After the vaccine completes these laboratory tests successfully, the FDA approves its use in clinical studies on human subjects. Participation in these studies is completely voluntary. Many individuals choose to contribute their time and energy for the advancement of science. Before they participate in research, all participants must demonstrate that they understand the purpose of the study and its potential risks. Volunteers agree to receive the vaccine and undergo any medical testing necessary to assess its safety and efficacy. [7]

Vaccine licensing is a lengthy process that may take 10 years or longer. The FDA requires that vaccines undergo three phases of clinical trials with human subjects before they can be licensed for use in the general public:

Phase one trials are small, involving only 20 to 100 volunteers, and last only a few months. The purpose of phase one trials is to evaluate basic safety and identify very common reactions.

Phase two trials are larger and involve several hundred participants. These studies last anywhere from several months to two years and collect additional information on safety and efficacy. Data gained from phase two trials can be used to determine the composition of the vaccine, how many doses are necessary, and a profile of common reactions.

Unless the vaccine is ineffective or causes health problems, the trials are expanded to phase three, which involves several hundred to several thousand volunteers. Typically these trials last several years. Because the vaccinated group can be compared to those who have not received the vaccine, researchers are able to identify true reactions. [1, 3, 7, 8, 9]

If the clinical trials demonstrate that the vaccine is safe and effective, the manufacturer applies to the FDA for two licenses: one for the vaccine (product license), and one for the production plant (establishment license). During the application process, the FDA reviews the clinical trial data and proposed product labeling. In addition, the FDA inspects the plant and goes over manufacturing protocols to ensure vaccines are produced in a safe and consistent manner. Only after the FDA is satisfied that the vaccine is safe is it licensed for use in the general population. [8]

Monitoring Vaccine Safety: Post-Licensing

After a vaccine is licensed for public use, its safety is monitored continually. The FDA requires all manufacturers to submit samples from each vaccine lot prior to its release. In addition, the manufacturers must provide the FDA with their test results for vaccine safety, potency, and purity. Each lot must be tested because vaccines are sensitive to environmental factors like temperature, and can be contaminated during production. The FDA rarely has recalled vaccine lots, for concerns such as mislabeling, contamination during production, and potential manufacturing problems at a production plant. [8]

While clinical trials provide important information on vaccine safety, the data are somewhat limited because of the relatively small number (hundreds to thousands) of study participants. Rare side effects and delayed reactions may not be evident until the vaccine is administered to millions of people. Therefore, the federal government established a surveillance system to monitor adverse events following vaccination. This project is known as the Vaccine Adverse Event Reporting System (VAERS). In addition, large-linked databases containing information on millions of individuals have been created to study rare vaccine adverse events. [1, 3]

Improvements in Vaccine Safety

In the last decades, numerous changes in vaccine production and administration have reduced the number of side effects and resulted in safer vaccines.

A more purified acellular pertussis (aP) vaccine has been licensed for use and has replaced the whole cell pertussis vaccine used in DTP (diphtheria, tetanus, pertussis vaccine). Several studies have evaluated the safety and efficacy of DTaP as compared to DTP and concluded DTaP is effective in preventing disease, and mild and serious side effects occurred less frequently when the DTaP vaccine was given. [3]

Changes in the schedule of polio vaccines also have resulted in fewer reports of serious adverse events. In 1997, the Advisory Committee on Immunization Practices recommended a change in the vaccination schedule to include sequential administration of inactivated polio vaccine (IPV) and oral polio vaccine (OPV). [10] This sequential schedule was expected to produce a high level of individual protection against the disease caused by wild polio virus, while reducing by 50 to 70% vaccine-associated paralytic polio (VAPP) that occurs in 8–10 people a year who receive OPV. [10] Today, only IPV is on the recommended childhood immunization schedule.

The Future of Vaccine Safety

The importance of vaccine safety will continue to grow throughout the 21st century. The development and licensure of new vaccines will add to the already robust immunization schedule. Scientists may also perfect new ways of administering immunizations including edible vaccines and needleless injections. However they are formulated or delivered, vaccines will remain the most effective tool we possess for preventing disease and improving public health in the future.


1. Chen RT, Hibbs B. Vaccine safety: Current and future challenges. Pediatric Annals1998;27(7):445–455.

2. Ellenberg SS, Chen RT. The complicated task of monitoring vaccine safety. Public Health Reports 1997;112(1):10–20.

3. Centers for Disease Control and Prevention. (1997) "Epidemiology and prevention of vaccine-preventable diseases, vaccine safety" (chapter 15). Washington DC: Government Printing Office.

4. Freed GL, Katz SL, Clark SJ. Safety of vaccinations: Miss America, the media, and public health.Journal of the American Medical Association 1996;276(23):1869–1872.

5. Brink EW, Hinman AR. The vaccine injury compensation act: The new law and you.Contemporary Pediatrics 1989;6(3):28–32, 35–36, 39, 42.

6. Howson CP, Howe CJ, Finchere HV, eds. Institute of Medicine. Adverse effects of pertussis and rubella vaccines: A report of the Committee to Review the Adverse Consequences or Pertussis and Rubella Vaccines. Washington, DC: National Academy Press, 1991.

7. Stratton KR, Howe CJ, Johnsion RB, eds. Adverse events associated with childhood vaccines; Evidence bearing on causality. Washington, DC; National Academy Press, 1994.

8. Understanding Vaccines [PDF - 393 KB]. Bethesda, MD; National Institutes of Health, 2008.

9. Food and Drug Administration (FDA).

10. Advisory Committee on Immunization Practice (ACIP). Poliomyelitis prevention in the United States: Introduction of a sequential vaccination schedule of inactivated poliovirus vaccine followed by oral poliovirus vaccine. MMWR 1997;46(RR-3);1–25.




Updated 10/16/15

This website is supported by an independent educational grant from Merck and an educational grant from Sanofi Pasteur U.S. 
ACOG does not allow companies to influence its programs, publications, or advocacy positions.