DATE: March 11, 2008
FROM: Karen Farizo, M.D., Committee Chair, Vaccines Clinical Trials Branch, DVRPA, OVRR, CBER
THROUGH: Lucia Lee, M.D., Team Leader, Vaccines Clinical Trials Branch, DVRPA, OVRR, CBER
TO: STN 103666/5158
RE: Approval Recommendation
Manufacturer and Product:
Sanofi Pasteur Limited, DAPTACEL [Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed]
DAPTACEL was approved for active immunization against diphtheria, tetanus, and pertussis in infants and children 6 weeks through 6 years of age on May 14, 2002. The currently approved dosing regimen for DAPTACEL is a four dose series, with a single dose administered at 2, 4, 6, and 15-20 months of age. The May 14, 2002 approval letter included a post-marketing commitment to conduct a clinical study to assess the use of DAPTACEL as a fifth dose at 4-6 years of age following four previous doses of DAPTACEL. With this Supplement, STN 103666/5158, the applicant has submitted the results of a study that evaluated the use of a fifth consecutive dose of DAPTACEL in children 4-6 years of age and is requesting approval of a fifth consecutive dose of DAPTACEL.
This Supplement contains the clinical report of a U.S. study in which children 4-6 years of age received a dose of DAPTACEL following four previous doses of either DAPTACEL (487 subjects) or Pentacel [Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine, Sanofi Pasteur Limited] (162 subjects). Although Pentacel is not currently approved in the U.S., safety data on subjects who previously received Pentacel were considered supportive in the evaluation of a fifth consecutive dose of DAPTACEL. The clinical study report includes safety and immunogenicity data, although for DTaP vaccines already approved for a primary series, CBER has not required immunogenicity data for the evaluation of booster doses following previous doses of the same vaccine.
The clinical study was reviewed, as well as a revised package insert that included relevant new data. Following exchange of information and discussions between CBER and the applicant, the package insert was modified and found to be acceptable by the review committee. The review committee concluded that the available safety data in this Supplement, combined with previous clinical experience in subjects who received three or four consecutive doses of DAPTACEL, support approval of a fifth consecutive dose of DAPTACEL and recommends approval of this Supplement. There are no requests for additional post-marketing studies associated with approval of this Supplement.
Pediatric Research Equity Act Requirements:
In their 2/5/08 meeting, FDA's Pediatric Review Committee concurred with the Supplement review committee's recommendation to grant waivers for studies of DAPTACEL in infants from birth to 6 weeks of age and in children and adolescents 7 to 16 years of age.