Diphtheria & Tetanus Toxoids & Pertussis Vaccine Adsorbed & Haemophilus b Conjugate Vaccine (Diph-theria CRM197 Protein Conjugate) - Tetra-mune; DTP + Hib
Status: withdrawn from the market
Organizations involved:
Lederle Labs. – Former
Wyeth – Parent; Former
Cross ref: See the entries for Diphtheria and Pertussis Toxoids and Pertussis Vaccine (DTP/DTaP) Products (#429); Tetanus Toxoid Products (#543); Diphtheria Toxoid Products (#418); and Haemophilus b Vaccine Products entry (#454). See the entry for Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) or HibTITER (#457), a component of this vaccine. See the entry for Lederle’s DTP vaccine (Tri-Immunol) (#449) for further information about the diphtheria and tetanus toxoid and pertussis (DTP) combination vaccine component of this vaccine.
Description: Diphtheria & Tetanus Toxoids & Pertussis Vaccine Adsorbed & Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) or Tetramune is an aqueous formulation of a quadravalent combination vaccine manufactured by mixing of a DTP vaccine (Tri-Immu-nol) with Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) or HibTITER, both from Lederle/Wyeth. The DTP contains diphtheria toxoid and tetanus toxoid and whole-cell pertussis vaccine adsorbed on aluminum phosphate.
The vaccine was supplied in multiple-use vials containing 5 mL and packages of 5 single-use 0.5 mL vials for intramuscular injection only. Each single dose of 0.5 mL of Tetramune contained 12.5 Lf of diphtheria toxin and 5 Lf of tetanus toxoid (with both inducing not less than 2 units of antitoxin per mil in the guinea pig potency test), 10 µg of purified Hib saccharide, and approximately 25 µg of CRM197 protein. Each 0.5 mL dose was formulated to contain less than 16 OPUs of inactivated pertussis cells. The total human immunizing dose (first three 0.5 mL inoculations) contained an estimated 12 units of pertussis vaccine with an estimated four protective units per dose, as determined by the mouse pertussis potency test. The product contained no more than 0.02% free formaldehyde; and less than 0.85 mg of aluminum per 0.5 mL dose. Thimerosal (mercury-based antimicrobial preservative; see #939) was used as a preservative at a final concentration of 1:10,000. The dating period was 23 months from the date of manufacture when stored at 2-8˚C (refrigerated). This includes five months for the bulk concentrate in manufacturer’s cold storage, plus an additional 18 months for the final fill product in vials. The date of manufacture is the date of the earliest valid potency test, regardless of which component of the final bulk product is tested first.
Nomenclature: DTP & Hib Vaccine/Lederle [BIO]; Tetramune [TR]; Diphtheria & Tetanus Toxoids & Pertussis Vaccine Adsorbed & Haemophilus b Conjugate Vaccine (Diph-theria CRM197 Protein Conjugate) [FDA]; NDC 0005-1960-31 [NDC]
Companies.: The Tetanus Toxoid Adsorbed, Diphtheria Toxoid Adsorbed and Pertussis Vaccine components and the formulated DTP vaccine were manufactured by Lederle Labs. (Pearl River, NY; formerly a subsidiary of American Cyanamid Co.), FDA CBER est. no. 0017, now merged into Wyeth. Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) was originally developed by Praxis Biologics, Inc., now a subsidiary of Wyeth, and manufactured at Lederle/Wyeth (formerly Praxis) facilities in Sanford, NC.
Tetramune was marketed in the U.S. and, perhaps, internationally by Wyeth and affiliates.
Manufacture: The adsorbed diphtheria, pertussis and tetanus components were manufactured independently and then combined to form DTP vaccine at Lederle Labs./Wyeth facilities in Pearl River, NY. Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) is manufactured at a Lederle/Wyeth, formerly Praxis Biologics, facility in San-ford, NC. Hib and DTP were combined at Lederle/Wyeth’s Pearl River, NY, facilities.
The finished product was tested for diphtheria and tetanus potency in guinea pigs, pertussis component potency in mice, and Haemophilus b conjugate potency by measuring total ribitol using a gas chromatographic method. Lack of toxicity of the pertussis component was determined by Mouse Toxicity Test. Thimerosal, aluminum content, free formaldehyde content, sterility and general safety were determined. The identity of the diphtheria, tetanus, pertussis and Hib components were measured.
The final vaccine was considered free from toxicity if it passes the Mouse Toxicity Test. At the end of 72 hours after administration, the average weight/mouse must be no less than the average weight/mouse before the injection, and at the end of 7 days; the average gain per mouse must be no less than 3.0 grams; and the vaccine-related death rate does not exceed 5%.
FDA class: Biologic PLA
CBER class: Multiple Antigen Preparations
Approvals: Date = 19930330; first approval; PLA/ELA ref. no. 92-0002 and 92-0003
Status: In Jan. 2001, Wyeth announced it was discontinuing manufacture of vaccines containing tetanus toxoid. The product license was voluntarily withdrawn.
Tech. transfer: U.S. patent 4,196,192, “Combined Haemo-philus influenzae type b and pertussis vaccine,” April 1, 1980, is assigned to American Cyanamid Co. (Lederle Labs.), which was acquired by American Home Products Corp., now Wyeth.
Trials: In clinical trials in infants and toddlers, the percent of clinically significant antibody titers for each of the vaccine components was greater than or equal to the response following separate administration of DTP (Tri-Immunol) and Haemophilus b conjugate (HibTITER) vaccines.
Companies involvement:
Full monograph
451 DTP & Hib Vaccine/Lederle
Nomenclature:
DTP & Hib Vaccine/Lederle [BIO]
Tetramune [TR]
Diphtheria & Tetanus Toxoids & Pertussis Vaccine Adsorbed & Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) [FDA]
NDC 0005-1960-31 [NUM NDC]
FDA Class: Biologic PLA
Year of approval (FDA) = 1993
Date of 1st FDA approval = 19930330
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
vaccines, bacterial
vaccines, combination
vaccines, toxoids (inactivated toxins)
bacterial culture <!-- bacterialculture -->
Bordetella pertussis
Clostridium tetani
Corynebacterium diphtheriae
Mueller and Miller medium
aluminum phosphate
Bacillus anthracis prophylaxis
Corynebacterium diphtheriae CRM197 protein
CRM197 protein
Diphtheria Toxoid
formaldehyde
Haemophilus influenzae type b capsular polysaccharide (PRP)
Pertussis Vaccine Adsorbed
polymyxin
polysaccharides
Tetanus Toxoid
thimerosal (mercury derivative)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
North American coral snake
North American coral snake
EU000 Not yet/Never filed with EU
UM999 Not Available/Not Marketed in US
US011 Approved Formerly in US/withdrawn
EM999 Not Available/Not Marketed in EU
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