History of Vaccine Safety (Archived)This page was last updated on October 9, 2009
- National Childhood Vaccine Injury Act
- Monitoring Vaccine Safety: Pre-Licensing
- Monitoring VAccine Safety: Post-Licensing
- Vaccine Adverse Event Reporting System
- Understanding Vaccine Safety Information from VAERS
- Vaccine Safety Datalink Project
- National Vaccine Injury Compensation Program
- Improvements in Vaccine Safety
- Risk Communication
- Conclusion: The Future of Vaccine Safety
Perhaps the greatest success story in public health is the reduction of infectious disease resulting from the use of vaccines. Routine immunization has eradicated smallpox from the globe and led to the near elimination of wild polio virus. Vaccines have reduced some preventable infectious diseases to an all-time low, and now few people experience the devastating effects of measles, pertussis, and other illnesses. Prior to approval by the Food and Drug Administration (FDA), vaccines are tested extensively by scientists to ensure they are effective and safe. Vaccines are the best defense we have against infectious diseases; however, no vaccine is 100% safe or effective. Differences in the way individual immune systems react to a vaccine account for rare occasions when people are not protected following immunization or when they experience side effects.
As the incidence of infectious diseases continues to decline, some people have become less interested in the consequences of preventable illnesses like diphtheria and tetanus. Instead, they have become increasingly concerned about the risks associated with vaccines. After all, vaccines are given to healthy individuals, many of whom are children, and therefore a high standard of safety is required. Since vaccination is such a common and memorable event, any illness following immunization may be attributed to the vaccine. While some of these reactions may be caused by the vaccine, many of them are unrelated events that occur after vaccination by coincidence. Therefore, the scientific research that attempts to distinguish true vaccine side effects from unrelated, chance occurrences is crucial. This knowledge is necessary to maintain public confidence in immunization programs. As science continues to advance, we strive to develop safer vaccines and improve delivery to protect ourselves against disease more effectively.
National Childhood Vaccine Injury Act
The topic of vaccine safety became prominent during the mid-1970's with increases in lawsuits filed on behalf of those presumably injured by the diphtheria, pertussis, tetanus (DPT) vaccine. Legal decisions were made and damages awarded despite the link of scientific evidence to support vaccine injury claims. As a result of these decisions, liability and prices soared, and several manufacturers halted production. A vaccine shortage resulted and public health officials became concerned about the return of epidemic disease. To reduce liability and respond to public health concerns, Congress passed the National Childhood Vaccine Injury Act (NCVIA) in 1986. This act was influential in many ways.
- The National Vaccine Program Office (NVPO) coordinates immunization-related activities between all Department of Health and Human Services (HHS) agencies, including the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), National Institutes of Health (NIH), and the Health Resources and Services Administration (HRSA).
- The NCVIA requires all health care providers who administer vaccines containing diphtheria, tetanus, pertussis, polio, mumps, rubella, hepatitis B, Haemophilus influenza type B, and varicella to provide a vaccine information statement (VIS) to the vaccine recipient, or his or her legal guardian, prior to each dose. A VIS must be given with every vaccination including each does in a multi-dose series. Each VIS contains a brief description of the disease as well as the risks and benefits of the vaccine. CDC develops VISs and distributes them to state and local health departments as well as individual providers.
- The NCVIA also requires health care providers to report certain adverse events (health effects occurring after immunization that may or may not be related to the vaccine) following vaccination to the Vaccine Adverse Event Reporting System (VAERS).
- Under the NCVIA, the National Vaccine Injury Compensation Program (NVICP) was created to compensate those injured by vaccines on a "no fault" basis.
- The NCVIA established a committee from the Institute of Medicine (IOM) to review the literature on vaccine side effects. This group concluded that there are limitations in our knowledge of the risks associated with vaccines. Of the 76 side effects they reviewed for a causal relationship, 50 (66%) had no or inadequate research to form a conclusion. Specifically, the IOM identified the following problems:
- Limited understanding of biological processes that underlie adverse events.
- Incomplete and inconsistent information from individual reports.
- Poorly constructed research studies--not enough people enrolled for the period of time.
- Inadequate systems to track vaccine side effects.
- Few experimental studies published in the medical literature. Significant progress has been made over the past few years to monitor side effects and conduct research relevant to vaccine safety.
Monitoring Vaccine Safety: Pre-Licensing
Before vaccines are licensed by the FDA, they are tested extensively in the laboratory and with human subjects to ensure their safety. First, computers are used to predict how the vaccine will interact with the 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 the studies is completely voluntary. Many individuals choose to contribute their time and energy for the advancement of science. Informed consent is obtained from all participants before they become involved in research. This ensures that they understand the purpose of the study and its potential risks, and are willing to participate. Volunteers agree to receive the vaccine and undergo any medical testing necessary to assess its safety and efficacy.
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 for only a few months. The purpose of Phase one trials is to evaluate basic safety and identify very common side effects. 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 side effects. Unless the vaccine is completely ineffective or causes serious side effects, 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 side effects.
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.
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. During the last 10 years, the FDA has recalled only three vaccine lots: one was mis-labled, another was contaminated during production, and the third was recalled after the FDA discovered potential manufacturing problems at a production plant.
While clinical trials provide important information on vaccine safety, the data are somewhat limited because of the 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). More recently, large-linked databases containing information on millions of individuals have been created to study rare vaccine adverse events.
Vaccine Adverse Event Reporting System
The National Childhood Vaccine Injury Act of 1986 requires health care providers to report certain adverse events that occur following vaccination. As a result, the Vaccine Adverse Event Reporting System was established by CDC and FDA in 1990. VAERS provides a mechanism for the collection and analysis of adverse events (side effects) associated with vaccines currently licensed in the United States. Adverse events are defined as health effects that occur after immunization that may or may not be related to the vaccine. VAERS data are monitored continually to detect unknown adverse events or increases in known side effects.
In 2008, VAERS received more than 25,000 reports of adverse events in the United States. Of these, 9.5% were reported as serious events causing disability, hospitalization, life-threatening illness, or death. Anyone can file a VAERS report, including health care providers, manufacturers, and vaccine recipients or their parents or guardians. Those who have experienced an adverse reaction following immunization are encouraged to seek help from a health care professional when filling out the form.
VAERS forms can be obtained in several ways. Each year the form is mailed to more than 200,000 physicians specializing in pediatrics, family practice, internal medicine, infectious diseases, emergency medicine, obstetrics, and gynecology. In addition, copies are sent to health departments and clinics that administer vaccines. The VAERS form requests the following information:
- The type of vaccine received
- The timing of vaccination
- The onset of the adverse event
- Current illnesses or medication
- History of adverse events following vaccination
- Demographic information about the recipient (age, gender, etc.)
A contractor, under the supervision of FDA and CDC, collects the information and enters it into a database. Those reporting an adverse event to VAERS receive a confirmation letter by mail indicating that the form was received. This letter contains a VAERS identification number. Additional information may be submitted to VAERS using the assigned identification number. Selected cases of serious adverse reactions are followed up at 60 days and one year post-vaccination to check the recovery status of the patient. The FDA and CDC have access to VAERS data and use this information to monitor vaccine safety and conduct research studies. VAERS data (minus personal information) are also available to the public.
The FDA reports that five cases of Kawasaki syndrome have been identified in children less than 1 year of age who received RotaTeq vaccine during clinical trials conducted before the vaccine was licensed. Three reports of Kawasaki syndrome were detected following the approval in February 2006 through routine monitoring using the Vaccine Adverse Event Reporting System (VAERS). After learning about these Kawasaki syndrome reports, CDC identified one additional unconfirmed case through its Vaccine Safety Datalink (VSD) project. The vaccine label has been revised to notify healthcare providers and the public about the reports of Kawasaki syndrome following RotaTeq vaccination.
The number of Kawasaki syndrome reports does not exceed the number of cases we expect to see based on the usual occurrence of Kawasaki syndrome in children. There is no known cause-and-effect relationship between receiving RotaTeq or any other vaccine and the occurrence of Kawasaki syndrome.
The available data support the safety of the RotaTeq vaccine and its effectiveness in preventing rotavirus infection, a common cause of severe infant diarrhea and hospitalization. CDC and FDA continue to monitor the safety of RotaTeq and all vaccines.
- CDC is not changing its immunization policy at this time. The available data support the safety and effectiveness of the RotaTeq vaccine in preventing rotavirus infection. CDC continues to support the recommendations of the Advisory Committee on Immunization Practices (ACIP) for routine immunization of all U.S. Infants with three doses of RotaTeq administered orally at ages 2, 4, and 6 months.
- It is important to remember that the known benefits of the RotaTeq vaccine in preventing rotavirus disease--the cause of one of our most common and potentially severe childhood illnesses-outweigh any known risks to date. Rotavirus causes severe diarrhea, vomiting, fever, and dehydration (gastroenteritis) in infants and young children. It is the leading cause of gastroenteritis in infants and children worldwide. Each year in the United States, rotavirus is responsible for more than 400,000 doctor visits, more than 200,000 emergency department visits, 55,000 to 70,000 hospitalizations, and between 20 and 60 deaths among children less than 5 years of age.
- Approximately 6 million doses of RotaTeq have been distributed in the United States through June 8, 2007. The three Kawasaki syndrome reports submitted to VAERS since the vaccine's licensure on February 3, 2006 do not exceed the number of cases we expect to see based on the usual occurrence of Kawasaki syndrome in children.
- As of June 13, 2007, CDC's VSD project reported one unconfirmed case of Kawasaki syndrome within 30 days of RotaTeq vaccination among 65,000 doses administered to children less than 1 year of age who are enrolled in the VSD project. This case has not been reported to VAERS. The VSD finding does not represent an increased risk over what would be expected to occur naturally among children less than 1 year of age who did not receive RotaTeq. VSD will continue to monitor for Kawasaki syndrome following RotaTeq vaccination.
- The RotaTeq label has been updated to include six specific cases of Kawasaki syndrome that were observed during the clinical trials conducted before the vaccine was licensed. There were five cases among the 36, 150 recipients of RotaTeq and one case among the 35,536 placebo recipients. It is not known if RotaTeq played a role in these cases. Additionally, the label has been revised to include information that VAERS has received reports of Kawasaki syndrome. Since licensure on February 3, 2006, three reports of Kawasaki syndrome have been submitted to VAERS. In the VAERS reports, the children had received other childhood vaccines in addition to RotaTeq.
- Kawasaki syndrome is a serious illness in children of unknown cause and characterized by a high fever that last several days. Kawasaki syndrome causes inflammation of the walls of the small- and medium- sized arteries (vasculitis) throughout the body, including the coronary arteries. Kawasaki syndrome primarily occurs in young children, most under 5 years of age. It affects approximately 4,000 children in the United States each year. There is no specific test to diagnose Kawasaki syndrome. A doctor diagnoses Kawasaki syndrome based on the presence of typical signs and symptoms. These include a high fever that lasts for five or more days, irritability, red eyes, bright red and cracked lips, a "strawberry" tongue, swollen hands and feet, peeling skin on the fingertips and toes, a rash, and swollen lymph nodes. Prompt recognition of symptoms and appropriate treatment are essential in the care of Kawasaki syndrome.
- Kawasaki syndrome has been seen after a variety of infectious or environmental exposures, including a prior respiratory illness, exposure to carpet-cleaning chemicals, use of a humidifier, and living near a body of water. There is no firm evidence that Kawasaki syndrome is caused by any of these factors. Kawasaki syndrome has not been linked to vaccination.
- CDC and FDA continue to monitor the safety of RotaTeq and all vaccines, and encourage health care providers and other individuals to report uses of Kawasaki syndrome or other severe medical problems following vaccinations to VAERS. For a copy of the vaccine reporting from, call 1-800-822-7967 or visit VAERS.
Related flu links can be found in the Vaccine Safety Resource Library.
Related Scientific Articles
Related scientific articles can be found in the Vaccine Safety Research/Publications section.