A Commitment to Safety
On the surface, it may seem that approaching vaccine safety as a continuous process--always looking into problems and potential problems--implies that vaccines are unsafe. "But it's actually a reflection of our ongoing commitment to safety, and to assuring the prevention of potentially lethal infectious diseases," says Jesse Goodman, M.D., M.P.H., deputy director for medicine at CBER. "It's also the nature of science to seek and implement improvements which make for safer and more effective medical products."Since 1996, for example, CBER has licensed several acellular pertussis vaccines. Acellular pertussis vaccines use only parts of the disease-causing bacteria and are associated with fewer side effects than the whole cell pertussis vaccines that had been in use. In 1997, the CDC's Advisory Committee on Immunization Practices (ACIP) recommended a switch from using the whole cell pertussis component of the diphtheria, tetanus, pertussis (DTP) vaccine to using acellular pertussis vaccines for all five doses in the childhood schedule (see "Recommended Childhood Immunization Schedule").
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.
