Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed - Adacel; dTpa; Tdap
Status: approved and marketed in U.S.
Organizations involved:
Sanofi Pasteur Ltd. – Manuf.; R&D; Tech.
Sanofi Pasteur Inc. – USA mark.
Sanofi Pasteur S.A. – Intl. mark.; Parent
Cross ref: See the entries for Acellular Pertussis Vaccine Products entry (#506); Diphtheria and Pertussis Toxoids and Pertussis Vaccine (DTP/DTaP) Products (#429); Tetanus Toxoid Vaccines (#543); and Diphtheria Toxoid Products (#418). See the entry (#430) for Daptacel.
Description: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed or Adacel is a diptheria, tetanus and acellular pertussis (dTpa; DTaP-like) vaccine with reduced (booster) doses of component antigens to be used as a booster vaccine in adults and children aged 11 years through 64 previously vaccinated against these diseases. The vaccine is a sterile, cloudy, uniform suspension of tetanus and diphtheria toxoids adsorbed on aluminum phosphate, combined with component pertussis vaccine and suspended in water for injection. Component pertussis vaccine is an acellular pertussis vaccine composed of five purified pertussis antigens. Adacel, like Daptacel, is a thimerosal (mercury-based preservative; see #939)-free formulation.
Adacel contains as active ingredients five acellular B. pertussis antigens [pertussis toxoid (PT), 2.5 µf; filamentous hemagglutinin (FHA), 5 µg; pertactin (PRN) 3 µg and; fimbriae agglutinogen (Agg) types 2 and 3, 5 µg]; diphtheria toxoid, 2 Lf; and tetanus toxoid; 5 Lf, with each component vaccine adsorbed onto aluminum adjuvant. Relative to Daptacel, Adacel contains half the amount of PT and FHA, the same amounts of the other pertussis antigens; 5 vs. 5 Lf of tetanus toxoid; and 2 vs. 15 Lf of diphtheria toxoid. Total aluminum phosphate content is 1.5 mg (total aluminum content is 0.33 mg); ≤5 ng residual formaldehyde; and <50 ng residual glutaraldehyde; and 3.3 mg (0.6% ± 0.1% v/v) 2-phenoxyethanol as preservative. Adacel packaged in vials containing 0.5 mL, in boxes containing five vials. Adacel is stored at 2-8˚C (refrigerated). The dating period is 36 months from the date of the manufacture of the final bulk when stored at 2- 8°C (refrigerated). The date of manufacture is defined as the date of final formulation of the final bulk.
Nomenclature: dTpa booster/GSK [BIO]; Adacel [TR]; Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed [FDA]; Tdap [SY]; dTpa [SY]; NDC 49281-400-05, NDC 49281-400-10 [NDC]
Companies.: Adacel was developed and is manufactured by Sanofi Pasteur Ltd., CBER/FDA est. no. 1726 (formerly Aventis Pasteur Ltd.), a subsidiary of Sanofi Pasteur S.A. It is marketed in the U.S. by Sanofi Pasteur Inc. (formerly Aventis Pasteur Inc.), and internationally by Sanofi Pasteur S.A. and affiliates.
FDA class: Biologic BLA
CBER class: Vaccines
Approvals: Date = 20050610; original BLA
Date = 20060123; BLA supplement; Indication = revised package insert
Date = 20080318; BLA supplement; Indication = include unit dose syringes as an alternate presentation
Date = 20090116; BLA supplement; Indication = revised the package insert regarding latex content
Indications: [full text of the "INDICATIONS AND USAGE” section of product insert/labeling, 3/27/2006]:
ADACEL vaccine is indicated for active booster immunization for the prevention of tetanus, diphtheria and pertussis as a single dose in
persons 11 through 64 years of age.
The use of ADACEL vaccine as a primary series, or to complete the primary series, has not been studied.
See DOSAGE AND ADMINISTRATION for use in tetanus prophylaxis in wound management.
ADACEL vaccine is not indicated for the treatment of B pertussis, C diphtheriae or C tetani infections.
As with any vaccine, ADACEL vaccine may not protect 100% of vaccinated individuals.
Status: On Aug. 11, 2004, GSK filed a BLA for Adacel use as a booster in those ages 11-64 having previously received a course of primary vaccination with each of the component vaccines. On March 15, 2005, the Vaccines and Related Biological Products Advisory Committee, FDA, voted unanimously to recommend licensure of Adacel for protection against tetanus, diphtheria and pertussis in adolescents and adults aged 11-64 years. The BLA was approved in June 6, 2005 (approval time = ~9.2 months), becoming the second dTpa vaccine to receive U.S. approval (in addition to Boostrix). Adacel was launched in the U.S. on July 25, 2005.
Adacel had been approved and marketed in Canada and Germany prior to U.S. approval. The vaccine has not received centralized European Union approval.
Trials: The BLA included studies in >7,200 participants in which the vaccine showed an excellent safety and immunogenicity profile. Adacel vaccine previously been approved and is marketed in Canada and Germany.
In a Phase III trial involving 749 individuals aged 12–54 years who had not been immunized against tetanus, diphtheria, or pertussis within the previous five years, 449 received a single 0.5 mL dose of Adacel and the other 300 received a dose of Td Adsorbed (tetanus toxoid) and of Component Pertussis (cP) Vaccine, given separately, one month apart. Four weeks following Adacel injection, of 446 individuals tested, 100% had tetanus antitoxin titres ≥0.10 IU/mL with a geometric mean titre of 15.7 IU/mL, while over 84% had diphtheria antitoxin titres ≥0.10 IU/mL (over 97% =0.01 IU/mL) with a geometric mean titre of 0.82 IU/mL. Pertussis antibody responses were comparable to those seen after a full 3-dose primary series with conventional DTaP vaccine in infants, or after a fourth dose (18 months of age) of Pentacel, a vaccine involving Haemophilus b Conjugate Vaccine (Tetanus Protein-Conjugate) reconstituted with Component Pertussis Vaccine and Diphtheria and Tetanus Toxoids Adsorbed Combined with Inactivated Poliomyelitis Vaccine (see related entry).
In a Phase III study in 2,043 adolescents between 11-17 years of age the immunogenicity of tetanus and diphtheria toxoids (Td vaccine) in adolescents was compared with Adacel (then licensed in Canada for booster immunization of adolescents and adults). Adacel and Td induced equivalent diphtheria and tetanus antibody responses. Adacel pertussis antibody responses were considered excellent, substantially exceeding those of infants given three doses of the analogous DTaP in a trial that demonstrated 85% efficacy against classic pertussis. Adacel’s side effects were comparable to those of tetanus boosters, including injection-site pain and low fevers, although adolescents reported those complaints more often with Adacel.
Medical: See entry #436 regarding the other U.S. dTpa vaccine.
dTpa vaccines, Adacel and Boostrix, are designed to be used in adolescents to reduce the increasing incidence of pertussis as immunity from a course of infant vaccination wanes.
Market: As reported by the National Immunization Program (NIP), Centers for Disease Control and Prevention (CDC; 7/2007), the Private Sector Cost/Dose (average cost) per dose is $37.43 for packages of 10 1-dose vials ($35.75 in 2006). The CDC Cost/Dose, the cost negotiated by NIP, CDC, for bulk contract purchase for public-sector state and local immunization programs, is $31.75 for packages of 10 1-dose vials ($30.75/dose in 2006; $12.75 in 2005). These prices include the $2.25/dose ($.75/covered component vaccine) Federal Excise Tax charged by the manufacturer for the federal vaccine injury compensation program. Sanofi Pasteur’s contract with NIP, CDC, expires on March 31, 2008.
First-half 2013 sales were $207 million. 2012 sales are estmates at about $400 million.
The 2007 Average Wholesale Price (AWP) is $444.60/10 single-dose vials, with a Direct Price (Manufacturer’s discount price) of $374.25/10 vials (Red Book, 2007).
The Sanofi Pasteur list price (Jan. 2006) is $335.00/10 1-dose vials ($33.50/dose). This does not include $2.25 ($.75/component vaccine) federal excise tax (funds vaccine liability insurance) charged by the manufacturer.
Another DTaP-type booster vaccine, Boostrix (see related entry below), competes against Adacel. Adacel was approved for a much broader age range than Boostrix.
Companies involvement:
Full monograph
437 dTpa booster/Sanofi
Nomenclature:
dTpa booster/Sanofi [BIO]
Adacel [TR]
Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed [FDA]
dTpa [SY]
Tdap [SY]
NDC 49281-400-05, NDC 49281-400-10 [NDC]
FDA Class: BLA biologic
Year of approval (FDA) = 2005
Date of 1st FDA approval = 20050610
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
vaccines, bacterial
vaccines, combination
vaccines, toxoids (inactivated toxins)
bacterial culture <!-- bacterialculture -->
Bordetella pertussis
Clostridium tetani
Corynebacterium diphtheriae
2-phenoxyethanol
alpha2-plasmin inhibitor
aluminum phosphate
Bordetella pertussis
Diphtheria Toxoid
filamentous hemagglutinin (FHA), Bordetella pertussis
pertussis toxin (PT)
Pertussis Vaccine Adsorbed, Acellular
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
EU200 Currently Approved in EU
UM001 Marketed Product in US
US200 Currently Approved in US
EM001 Marketed Product in EU
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