Status: approved; marketed

Organizations involved:

Sanofi Pasteur Inc. – Manuf.; R&D; Tech.; USA mark.

Sanofi Pasteur S.A. – Intl. mark.; Parent

Cross ref: See the entries for components of this vaccine – Tetanus Toxoid and Tetanus Toxoid Adsorbed, including those from Sanofi Pasteur. See also the entry for Td vaccine manufactured by Sanofi Pasteur Ltd. (Canada).

Description: Tetanus and Diphtheria Toxoids Adsorbed for Adult Use is an aqueous formulation of a suspension of formaldehyde-inactivated diphtheria and tetanus toxoids (inactivated toxin) precipitated with aluminum potassium sulfate (alum) adjuvant in an isotonic sodium chloride solution containing sodium phosphate buffer to control pH, with thimerosal, a mercury compound (see #939), added as an antimicrobial preservative. A thimerosal-free (i.e., thimerosal not added to the vaccine, but contains traces from manufacturing) formulation has been approved, but has not yet been launched.

Diphtheria toxin is obtained from Corynebacterium diph-theriae bacteria cultured in a modified Mueller and Miller medium. Tetanus toxin is obtained from Clostridium tetani cultured in a peptone-based medium containing a bovine extract (from U.S. source). Tetanus and diphtheria toxins are separately detoxified with formaldehyde, and purified by serial ammonium sulfate fractionation, and diafiltration. The tetanus and diphtheria toxoids induce at least 2 units and 0.5 units of antitoxin per mL, respectively, in the guinea pig potency test. The currently marketed vaccine contains thimerosal (a mercury derivative; see related entry) at a concentration of 1:10,000 as an antimicrobial preservative. The vaccine is stored at 2-8°C (35-46°F; refrigerated).

The current thimerosal-preserved vaccine is packaged in single-dose syringes containing 0.5 mL of vaccine, 10 syringes per package; and in 10-dose 5 mL vials for intramuscular injection only. Each 0.5 mL dose contains 5 Lf of tetanus toxoid, 2 Lf of diphtheria toxoid, and not more than 0.28 mg of aluminum by assay. As of April 2004, only the 10-dose 5 mL vials were available from the company.

The new thimerosal-free formulation contains the same toxoid antigens packaged in 0.5 mL single-dose vials (approved in Jan. 2003). Packaging in single dose Luer-Lok syringes (Decavac), sold in packages of ten 0.5 mL syringes, was approved in March 2004. This formulation contains a trace amount of residual thimerosal (≤0.3 µg mercury/dose) from the manufacturing (culturing) process. The single-dose syringes and 10-dose vials have an expiration dating period of 24 months when stored at 2-8˚C.

Nomenclature: Tetanus & Diphtheria Toxoids/Sanofi USA [BIO]; Tetanus and Diphtheria Toxoids Adsorbed for Adult Use [FDA]; Decavac [TR; for preservative-free prefilled syringes]; Tetanus and Diphtheria Toxoids Combined Aluminum Phosphate Precipitated [FDA former]; Td vaccine [SY CDC]; NDC 49821-800-83; NDC 49821-800-10 [NDC]; 49281-291-10 [NDC for Decavac]

Companies.: This vaccine is manufactured by Sanofi Pasteur Inc. (Swiftwater, PA), CBER/FDA lic. no. 0711, formerly Aventis Pasteur Inc. It is marketed in the U.S. by Sanofi Pasteur Inc., and perhaps internationally by Sanofi Pasteur S.A. Aventis merged into Sanofi Aventis S.A. in late 2004.

FDA class: Biologic PLA

CBER class: Multiple Antigen Preparations

Approvals: Date = 19550307; first approval, granted to Merrell-National Labs.

Date = 19780103; product license revoked and granted (reissued) under a new FDA proper name and to a new owner, Connaught Labs., Inc.

Date = 20030129; BLA supplement (BL 103919/5018); Indication = approval of a preservative (thimerosal)-free, single dose vial

Date = 20040324; BLA supplement (BL 103921/5031); Indication = approval of a preservative-free, single dose Luer-Lok syringe (DECAVAC)

Indications: [portion of the "INDICATIONS AND USAGE” section of product insert/labeling, 7/2004]:

DECAVAC vaccine is indicated for active immunization of persons 7 years of age or older for prevention of tetanus and diphtheria.

Status: Decavac was launched in the U.S. in 1st quarter 2005. This vaccine has not received centralized European Union approval.

Sanofi Aventis, the largest vaccine company, presumably manu-factures its own diphtheria toxoid vaccine components, but no diphtheria toxoid monovalent vaccine from the company is currently approved. Thus, the source for the approval of the diphtheria toxoid (D) component of this combination vaccine is unclear. The approval for this Td vaccine (or another vaccine, e.g., DTP or DTaP) from the company may effectively cover approval of the diphtheria toxoid component of this and other diphtheria toxoid-containing vaccines from the company.

Thimerosal (preservative)-free Decavac was launched in the U.S. on Jan. 18, 2005.

Trials: The efficacy of tetanus toxoid and diphtheria toxoid used in the preservative-free formulation was determined on the basis of immunogenicity studies, with a comparison to a serological correlate of protection (0.01 antitoxin units/mL) established by the Panel on Review of Bacterial Vaccines & Toxoids. A clinical study to evaluate serological responses and adverse reactions was performed in 58 individuals 6 years of age and older. The results indicated protective levels of antibody were achieved in greater than 90% of the study population after primary immunization with both components. Booster effects were achieved in 100% of the individuals with preexisting antibody responses.

Medical: Td vaccine is used only as a booster (not for primary immunization) of adults previously having completed a pediatric DTP/DTaP regimen of five doses, or otherwise having received tetanus vaccine at least 10 years prior.

Market: Total 2005 (first partial year) sales were $180 million.

The 2007 Average Wholesale Price (AWP) is $226.68 for 10 single-dose vials, with a Direct Cost (Manufacturer’s discount) of $160.00 for 10 vials (2005 Red Book). This include the $1.50/dose ($.75/covered component vaccine) Federal Excise Tax charged by the manufacturer for the federal vaccine injury compensation program.

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 $19.14 for packages of 10 single-dose vials or prefilled syringes ($18.30 in 2006; $17.50 in 2004). The CDC Cost/Dose, the cost negotiated by NIP, CDC, for bulk contract purchase for public-sector state and local immunization programs, is $17.38 for packages of 10 single-dose vials or prefilled syringes ($16.62 in 2006; $15.90 in 2004). Sanofi Pasteur’s contract with NIP, CDC, expires on March 31, 2008.

The Sanofi Pasteur list price (Jan. 2006) is $168.00/package of 10 prefilled syringes or single-dose vials, with a Direct Price (Manufacturer’s discounted price) of $191.40. This includes the federal excise tax of $1.50.