Diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, hepatitis B (recombinant) and Haemophilus influenzae type b conjugate vaccine, adjuvanted; HEXAVAC
Status: withdrawn in EU; not approved in U.S.
Organizations involved:
Sanofi Pasteur S.A. – Manuf.; R&D; Tech.
Merck & Co., Inc. – Manuf.
Sanofi Pasteur MSD – Europe mark.
Cross ref.: See the entries for Diphtheria Toxoid Products; Tetanus Toxoid Products; Pertussis Vaccines, Acellular; Hepatitis B Virus Vaccine Products; and Haemophilus influenzae Vaccine Products. See also the entry for Hepatitis B vaccine, rDNA/Merck (Recombivax HB). See DTaP-Hib-HBV, rDNA-IPV/GSK (Infanrix Hexa), another hexavalent vaccine with the same basic vaccine components.
Description: HEXAVAC is a hexavalent (6-antigen) combination vaccine containing diphtheria toxoid, tetanus toxoid, two acellular pertussis antigens, three strains of inactivated poliovirus (cultured in VERO African green monkey kidney cells), recombinant Saccharomyces cerevisiae (yeast)-expressed hepatitis B virus surface antigen (HBsAg); and Haemophilus influenzae type b conjugate (PRP-T), adsorbed on aluminum hydroxide adjuvant.
HEXAVAC is packaged in 0.5 mL prefilled syringes. Each 0.5 mL dose contains: diphtheria toxoid, ≥20 IU (30 Lf); tetanus toxoid, ≥40 IU (10 Lf); pertussis toxoid, 25 µg; pertussis filamentous hemagglutinin (FHA), 25 µg; recombinant hepatitis B virus surface antigen (HBsAg), 5.0 µg; inactivated poliovirus type 1 (Mahoney), 40 units D antigen; inactivated poliovirus type 2 (MEF 1) , 8 units D antigen; inactivated poliovirus type 3 (Saukett), 32 units D antigen; and Haemophilus influenzae type b polyribosylribitol phosphate (PRP), 12 µg, conjugated to tetanus toxoid, 24 µg; with these components adjuvanted on aluminum hydroxide, 0.3 mg. Excipients in the vaccine are disodium phosphate, monopotassium phosphate, sodium carbonate, sodium bicarbonate, trometamol, sucrose, Medium 199 (M-199; Hank’s medium; mixture of amino acids, mineral salts, vitamins and other ingredients), and Water for Injection. The vaccine has a shelf life of 36 months, when stored at 2-8˚C (refrigerated).
Nomenclature: DTaP-Hib-HBV, rDNA-IPV/Sanofi [BIO]; HEXAVAC [SY]; Diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, hepatitis B (recombinant) and Hemophilus influenzae type b conjugate vaccine, adjuvanted [EU common name]
Companies.: HEXAVAC is manufactured by Sanofi Pasteur S.A., CBER/FDA est. no. 1279, formerly Aventis Pasteur S.A. HEXAVAC is marketed in Europe by Sanofi Pasteur MSD, formerly Aventis Pasteur MSD, a joint venture of Sanofi Pasteur S.A. and Merck & Co., Inc.
Manufacture: All components are manufactured by Sanofi-Pasteur S.A. (Marcy L’Etoile, France), except for recombinant HBsAg vaccine, which is manufactured by Merck & Co., Inc. Preparation of the final bulk (blending of the six component vaccines) is performed by Sanofi-Pasteur S.A. (Marcy L’Etoile, France). Finished (blended) product is stored at 5˚C ± 3˚C. Since the vaccine contains aluminum hydroxide gel, it cannot be sterile filtered. All components of the vaccine are sterile and checked for sterility when produced.
Status: European Union (EU)-wide approval (MAA) was granted on Oct. 23, 2000.
In Sept. 2005, EMEA/EU suspended sales of Hexavac due to concerns it may not offer adequate protection (insufficient antibody responses) to its hepatitis B component. This was attributed to variability in the production process on the part of Merck. The efficacy of the other components in the formulation was not questioned. The agency requested Sanofi-Pasteur design a follow-up program to assess if children having received Hexavax will need to be revaccinated at a later stage. Glaxo-SmithKline responded by increasing production of Infanrix hexa (a similar competing hexavalent vaccine; see related entry).
Indications: [European Union]:
\“for primary and booster vaccination of children against diphtheria, tetanus, pertussis, hepatitis B caused by all known subtypes of virus, poliomyelitis and invasive infections caused by Haemophilus influenza type b.”
Medical: Primary vaccination involves intramuscular injection of two or three doses (0.5 mL) within the first year of life with at least one month between doses, e.g., at 2, 3, and 4 months or 3 and 5 months. This is followed by two booster doses between 11-13 months of age after two-dose primary vaccination; and one booster dose at 12-18 months after three-dose primary vaccination.
Market: Hexavac accounted for ~10% of Sanofi-Pasteur’s vaccine sales (before its withdrawal in the European Union).
Competition: In July 2008, EasyFive, a diphtheria, tetanus, pertussis, haemophilus influenza type b and hepatitis B vaccine from Panacea Biotec Ltd. (Mumbai, India) received World Health Organization (WHO/UN) prequalification (approval for purchase by interantional public heatlh programs and countries that use WHO prequalification as surrogate product approvals).
Index Terms:
Companies involvement:
Full monograph
440 DTaP-HBV, rDNA-Hib-IPV/Sanofi
Nomenclature:
DTaP-HBV, rDNA-Hib-IPV/Sanofi [BIO]
HEXAVAC [SY]
Diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, hepatitis B (recombinant) and Haemophilus influenzae type b conjugate vaccine, adjuvanted [EU common name]
FDA Class: Biologic BLA
biopharmaceutical products
conjugates
recombinant DNA
vaccines, bacterial
vaccines, combination
vaccines, toxoids (inactivated toxins)
adw, hepatitis B virus subtype
bacterial culture <!-- bacterialculture -->
Clostridium tetani
Clostridium tetani
Corynebacterium diphtheriae
filamentous hemagglutinin (FHA), Bordetella pertussis
Haemophilus influenzae b prophylaxis
hepatitis B virus (HBV)
media, serum-free
monkey diploid cells, fetal rhesus<!-- monkeycells -->
monkey diploid cells, fetal rhesus<!-- monkeycells -->
polio prophylaxis
poliovirus type 1
poliovirus type 2
Saccharomyces cerevisiae (yeast)
vegetable oil extraction
aluminum hydroxide
Diphtheria Toxoid
disodium phosphate
formaldehyde
Haemophilus influenzae type b
media, serum-free
monomethoxy polyethylene glycol (PEG)
pertactin (69 kDa protein)
Pertussis Vaccine Adsorbed, Acellular
polio prophylaxis
polymyxin
sodium bicarbonate
sodium bromide
Sterile Water for Injection
sucrose
Tetanus Toxoid
trisodium citrate
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
North American coral snake
North American coral snake
EU011 Approved Formerly in EU/withdrawn
UM999 Not Available/Not Marketed in US
US000 never filed/no plans
EM999 Not Available/Not Marketed in EU
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