Status: marketed in U.S.

Organizations involved:

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

Sanofi Pasteur S.A. – Parent

Cross ref: See the Tetanus Toxoid Products entry (#543), and the other Tetanus Toxoid entries. See also the combination vaccines, e.g., DTaP (Tripedia; entry #431), from Sanofi Pasteur incorporating this vaccine as a component.

Description: Tetanus Toxoid Adsorbed is an aqueous formulation of formaldehyde inactivated tetanus toxin (toxoid) vaccine obtained from fermentation of Clostridium tetani bacteria adsorbed on aluminum potassium sulfate (alum) adjuvant. The adsorbed toxoid is suspended in sodium chloride solution containing sodium phosphate buffer (0.85%); and in in multi-dose vials contains thimerosal (a mercury-based antimicrobial preservative; see related entry) added to a final concentration of 1:10,000. Each dose of thimerosal-containing vaccine delivers 25 µg mercury.

The vaccine is supplied in 10-dose, 5 mL vials. Each 0.5 mL dose contains 5 Lf (flocculation units) of tetanus toxoid and not more than 0.25 mg of aluminum. The residual formaldehyde content, by assay, is less than 0.02%. The tetanus toxoid induces at least 2 units of antitoxin per mL in the guinea pig potency test. The product is stored at 2-8°C (35-46°F; refrigerated).

A new single-dose, preservative-free formulation was approved in fall 2005. This is supplied in a unit dose 0.5 mL vial, and contains a trace amount of thimerosal (≤ 0.3 µg mercury/dose)] from the manufacturing process.

Nomenclature: Tetanus Toxoid Adsorbed/Sanofi [BIO]; Tetanus Toxoid Adsorbed [FDA USAN]; Tetanus Toxoid Aluminum Phosphate Precipitated [FDA former]; NDC 49281-800-83; NDC 49281-800-84 [NDC]

Companies.: The vaccine is manufactured by Sanofi Pasteur Inc. (Swiftwater, PA), FDA CBER est. no. 0711. It is marketed in the U.S. by Sanofi Pasteur Inc; and perhaps internationally by Sanofi Pasteur S.A. affiliates.

Manufacture: Clostridium tetani is cultured in a peptone-based (bovine-derived) medium and detoxified by incubation with formaldehyde. The resulting toxoid is purified by serial ammonium sulfate fractionation, followed by sterile filtration, adsorbed to aluminum potassium sulfate, diluted with physiological saline solution (0.85%), and thimerosal (a mercury derivative) is added to a final concentration of 1:10,000.

FDA class: Biologic PLA

CBER class: Toxoids And Toxins For Immunization

Approvals: Date = unknown (for original approval date)

Date = 19701015; first approval, PLA, granted to Merrell-National Labs.; according to the CBER/FDA database and other FDA sources; However, this is almost certainly the date on which the PLA was revoked and granted (reissued) under the current FDA proper name (the same as the other tetanus toxoid adsorbed-containing vaccines from the company for which documentation was available).

Date = 19780103; license revoked and granted (reissued) to Connaught Labs. Inc. (new owner)

Date = 19991209; license revoked and granted (reissued) to Aventis Pasteur Inc. (new owner)

Date = 20050923; BLA supplement; Indication = single dose vial formulation that is preservative (thimerosal)-free

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

Tetanus Toxoid Adsorbed vaccine is indicated for active immunization of children 7 years of age or older, and adults, against tetanus, wherever combined antigen preparations are not indicated. This vaccine should not be used for immunizing children below 7 years of age. In children below 7 years of age, either Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) – Tripedia, or Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed USP (For Pediatric Use) (DTP) is recommended. If a contraindication to pertussis immu-nization exists, the recommended vaccine is Diphtheria and Tetanus Toxoids Adsorbed (For Pediatric Use) (DT) ...[truncated]

Market: The Sanofi Pasteur list price (Jan. 2006) was $178.50/10 single-dose vials ($132.25 004, and $115.00 in Jan. 2003). A $.75/dose federal excise tax (funds vaccine liability insurance) is added to the sales price.

The 2007 Average Wholesale Price (AWP) is $232.42/10-dose vial ($167.70 in 2005), with a Direct Cost (Manufacturer’s discount) price of $194.93 ($139.75 in 2005) (Red Book, 2007). Prices include the $.75/dose federal excise tax charged by the manufacturer for the national vaccine compensation program.

This vaccine is not among those purchased in bulk through contracts by the National Immunization Program (NIP), Centers for Disease Control and Prevention (CDC), for public-sector state and local immunization programs. The programs favors use of DTaP vaccines.

As discussed in the Tetanus Toxoid Vaccines entry (#543), there have been repeated shortages of tetanus toxoid. Associated with this, prices have risen dramatically in recent years. Aventis Pasteur raised its price in 2000, noting that the vaccine was underpriced and manufacturing plants had to be upgraded. Prices rose from $14.50 per 5mL 10-dose vial in 1999 to $60.40 in 2000, and are now in the $180 range. Because cultures for the vaccine and the manufacturing process require about a year, production can easily get behind schedule and demand.

With the abandonment of tetanus toxoid manufacture by Wyeth (and its Lederle subsidiary) in Jan. 2001 and other companies, Sanofi Pasteur is now the major source for monovalent and other tetanus toxoid-containing vaccines in the U.S.