Vaccine Safety : Process, Concerns

by Food and Drug Administration (FDA)

(Page 2 of 4)

The National Institute of Allergy and Infectious Diseases (NIAID) sponsored clinical trials for some of the experimental acellular vaccines. "We set out to develop an improved vaccine that would be as effective as the standard whole cell vaccine but cause less extended crying, fevers, and other side effects," says Carole Heilman, Ph.D., director of NIAID's division of microbiology and infectious diseases. CBER scientists also played a critical role by developing methods to evaluate the acellular vaccines, which helped them get to clinical trials faster.

There have been other recent policy changes to improve vaccine safety, including ACIP's 1999 recommendation to change from the use of oral polio vaccine (OPV) to the inactivated polio virus (IPV). OPV had been highly effective in controlling naturally occurring polio outbreaks, preventing thousands of cases of paralysis a year. But as a live virus, it mutated in extremely rare cases to cause polio itself. Continued use of OPV resulted in about 10 cases of paralytic polio each year among millions vaccinated and their contacts, according to William Egan, Ph.D., deputy director of CBER's office of vaccine research and review. Switching to the use of IPV eliminated this risk and was appropriate once epidemic polio was controlled.

"There are times when we also take action even when there is just the theoretical potential for harm," Goodman says. Thimerosal, a mercury-containing compound, had been the most widely used preservative in vaccines. Its use in minute amounts helped to prevent bacteria from contaminating multi-dose vials of vaccines and other medicines, protecting against potentially serious infections. But thimerosal has been nearly eliminated from vaccines because of legitimate and growing scientific concerns about the possible effects of mercury on the nervous system, Goodman says.

"In addition, as the numbers of vaccines used in children have increased, small infants who received every recommended vaccine could be exposed to cumulative doses of mercury that exceeded some, but not all, federal guidelines," Goodman explains.

Even though there are no convincing data that show harm because of thimerosal in vaccines, the U.S. Public Health Service recommended moving rapidly to vaccines that are thimerosal-free. The FDA encouraged manufacturers to comply and set the highest priority for its reviews of such products, Goodman says. As a result, all recommended pediatric vaccines available are now thimerosal free or have greatly reduced thimerosal contents. In March 2001, the FDA approved a newly formulated version of Tripedia, a diphtheria and tetanus toxoids and acellular pertussis (DTAP) vaccine with only a trace amount of thimerosal.

A Thorough Process

The most common components of vaccines are weakened microbes (disease-causing microorganisms), killed microbes, and inactivated toxins. In addition, subunit vaccines, which only use a part of the bacterium or virus, are increasingly being used.

Manufacturers conduct stringent tests to make sure that cell lines used for producing viral vaccines do not contain adventitious agents (unwanted viruses) such as simian virus 40 (SV40), which was found in some early polio vaccines. These vaccines had been manufactured in kidney cells from simians (monkeys) that harbored SV40. Following its discovery, SV40 was removed from vaccines, and vaccines have been free of the virus since the early 1960s. CBER scientists are developing potentially better methods to detect such infectious agents.

Developing vaccines is a thorough and rigorous process, Egan says. Vaccines are tested for safety on animals first, and then in humans during several phases of clinical trials. The most important clinical trial for the recently licensed vaccine Prevnar involved nearly 40,000 people, equally divided between those who received the vaccine and those who did not. Prevnar was approved to prevent invasive pneumococcal diseases such as meningitis.

A group of FDA scientists reviews data and the proposed labeling of the vaccine, which includes directions for use and information about potential side effects. The committee also reviews manufacturing protocols, conducts its own tests, and inspects the manufacturing facility. The FDA's Vaccines and Related Biological Products Advisory Committee, which includes scientific experts and consumer representatives, can be consulted at any time to review data and recommend action to the agency.

After a vaccine is licensed, the FDA generally requires that manufacturers use validated methods to test samples from each vaccine lot for safety, potency, and purity prior to its release for public use. The FDA also tests selected lots and products to help assure the accuracy of tests conducted by the manufacturers.

Common Concerns

"Most vaccines cause some side effects, but they are usually minor and short-lived like low-grade fever and soreness at the injection site," Midthun says. Serious vaccine reactions — causing disability, hospitalization, or death — are extremely rare but they can happen.

Like any medicine, vaccines carry a small risk of serious harm such as severe allergic reaction. But experts point out that the risk of being harmed by a vaccine is much lower than the risk that comes with infectious diseases.

For example, in 1976, the swine influenza (flu) vaccine was associated with a severe paralytic illness called Guillain-Barré Syndrome (GBS). According to the CDC's vaccine information sheet on the influenza vaccine, "if there is a risk of GBS from current influenza vaccines, it is estimated at 1 or 2 cases per million persons vaccinated, much less than the risk of severe influenza, which can be prevented by vaccination." Each year, flu causes tens of thousands of deaths, mostly among older people. Most people who get the influenza vaccine have no serious problem from it.

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.