On August 27, 1999, Merck Vaccine Division* (Merck & Co., Inc., West Point, Pennsylvania) received approval from the Food and Drug Administration (FDA) of a supplement to Merck's license application to include the manufacture of single-antigen preservative-free hepatitis B vaccine (Recombivax HB®, Pediatric); distribution is expected to begin September 13, 1999. In addition, SmithKline Beecham Biologicals (SmithKline Beecham, Philadelphia, Pennsylvania), expects to make single-antigen preservative-free hepatitis B vaccine (Engerix-B®, Pediatric) available in the near future. Further product information will be provided when it becomes available. Product packaging and labels will indicate that these vaccines do not contain preservative.
To prevent shortages because of limited supplies of single-antigen hepatitis B vaccines that do not contain thimerosal as a preservative and to assure prevention of perinatal and early childhood hepatitis B virus (HBV) infection during the transition when both vaccines that contain and do not contain thimerosal as a preservative are available, the following three steps should be taken:
The priority for use of single-antigen hepatitis B vaccines that do not contain thimerosal as a preservative should be to vaccinate newborn infants. Routine hepatitis B vaccination policies for all newborn infants should be reintroduced immediately in hospitals in which these policies and practices have been discontinued. All hospitals should ensure that newborn infants of hepatitis B surface antigen (HBsAg)-positive mothers and of mothers whose HBsAg status is unknown receive their first dose of hepatitis B vaccine within 12 hours of birth. If hepatitis B vaccine that does not contain thimerosal as a preservative is not available, then thimerosal preservative-containing vaccine should be used for these infants.
When available, hepatitis B vaccines that do not contain thimerosal as a preservative should be used to vaccinate infants aged <6 months (single-antigen hepatitis B vaccine for infants aged <6 weeks and either single-antigen or combination products for infants aged greater than or equal to 6 weeks). Infants in groups at high risk for perinatal and early childhood HBV infections should complete the three-dose hepatitis B vaccine series by age 6 months. When vaccines that do not contain thimerosal as a preservative are not available, these groups should be vaccinated with thimerosal preservative-containing vaccine. For infants born to HBsAg-negative mothers and who are not in high-risk groups, existing recommendations should be used for administering thimerosal preservative-containing hepatitis B vaccines if vaccine that does not contain thimerosal as a preservative is not available.1- 4 These groups should complete the three-dose hepatitis B vaccine series by age 18 months.
Thimerosal preservative-containing hepatitis B vaccines can continue to be used for vaccinating children aged ≥6 months, adolescents, and adults as is recommended.1- 6
National Center for Infectious Diseases; National Immunization Program; Agency for Toxic Substances and Disease Registry; National Center for Environmental Health, CDC.
On July 8, 1999, the American Academy of Pediatrics (AAP) and the Public Health Service (PHS) released a joint statement about thimerosal in vaccines, and the American Academy of Family Physicians (AAFP) released a comparable statement.1- 3 Thimerosal is a mercury-containing preservative that has been used as an additive to biologics and vaccines since the 1930s because it is effective in preventing bacterial and fungal contamination, particularly in open multidose containers. Vaccine manufacturers, FDA, and other PHS agencies are working together to replace expeditiously thimerosal preservative-containing vaccines whenever possible with vaccines that do not contain thimerosal as a preservative while ensuring maintenance of high vaccination coverage levels and prevention of disease.
Previous recommendations for using thimerosal-containing vaccines indicated that clinicians and parents could take advantage of the flexibility in the immunization schedule to delay hepatitis B vaccination from birth until age 2-6 months for infants born to mothers who are HBsAg negative.1- 4 No changes were made in recommendations for immunization at birth of infants of HBsAg-positive mothers or infants of mothers with an unknown HBsAg status.
After the joint AAP/PHS statement on thimerosal, the AAP and CDC provided additional implementation guidance.3,4 CDC guidance included hepatitis B vaccination should be continued at birth for infants born to HBsAg-negative mothers belonging to populations or groups that have a high risk for early childhood HBV infection, including Asian/Pacific Islanders, immigrant populations from countries in which HBV infection is of high or intermediate endemicity,7 and households with persons with chronic HBV infection. To ensure the prevention of perinatal HBV transmission, hospitals should continue policies to vaccinate all infants at birth until procedures are in place to guarantee that (1) the HBsAg status of every pregnant woman is reviewed at delivery, (2) appropriate passive-active immunoprophylaxis (hepatitis B immune globulin and hepatitis B vaccine) is provided for infants of HBsAg-positive women within 12 hours of birth, and (3) appropriate active immunoprophylaxis (hepatitis B vaccine) is provided for infants of women with an unknown HBsAg status.
After the statements on thimerosal in vaccines were published, changes occurred in newborn hepatitis B vaccination policies and practices in some hospitals, including unintended changes affecting immunization of infants at risk for perinatal HBV transmission. In August 1999, state and territorial health department hepatitis coordinators conducted surveys of selected birthing hospitals in their project areas. Of 977 hospitals surveyed in 48 project areas, 773 (79%) were aware of the joint AAP/PHS statement on thimerosal. Of 574 hospitals that were aware of the statement and had existing policies or standing orders to vaccinate all newborns, 262 (46%) reported a policy change to no longer routinely vaccinate newborns of HBsAg-negative mothers. In addition, 52 (9%) reported they no longer routinely vaccinate any newborn (CDC, unpublished data, 1999). Such a policy usually requires a physician's order to vaccinate infants of HBsAg-positive mothers and infants of mothers whose HBsAg status is unknown. CDC also has received anecdotal reports of hospitals in which policies were changed, and infants born to HBsAg-positive mothers and infants born to mothers with unknown HBsAg status were not vaccinated within 12 hours of birth (CDC, unpublished data, 1999). Chronic HBV infection develops in approximately 90% of infants infected perinatally; among chronically infected infants, the risk for premature death from HBV-related liver cancer or cirrhosis is approximately 25%.8 The availability of hepatitis B vaccine that does not contain thimerosal as a preservative should alert medical facilities to review their policies to ensure the vaccination of newborns as recommended by the Advisory Committee on Immunization Practices, AAFP, and AAP.
Availability of Hepatitis B Vaccine That Does Not Contain Thimerosal as a Preservative. JAMA. 1999;282(13):1219–1220. doi:10.1001/jama.282.13.1219