Status: marketed in the U.S.,internationally, but not in the European Union

Organizations involved:

Merck & Co., Inc. – Manuf.; R&D; Tech.; USA mark.; World mark.

Cross ref: See the entries for component vaccines – Hepatitis B (Recombinant) Vaccine or Recombivax HB (#174), and Haemophilus b Conjugate (Meningococcal Protein Conjugate) or PedvaxHIB (#458), both from Merck & Co., Inc. See the entries for Hepatitis B Vaccine Products (#468) and Haemophilus b Vaccine Products (#453).

Description: Comvax refers to an aqueous formulation of bivalent vaccine designed solely for pediatric use, a combination of Haemophilus b Conjugate (Men-in--gococcal Protein Conjugate) or PedvaxHIB, and Hepa-titis B (Recombinant) Vaccine or Recom-bivax HB (pediatric formulation), both manufactured and marketed separately as monovalent vaccines by Merck & Co., Inc. The component vaccines are mixed and co-adjuvanted with aluminum hydroxide (alum). Comvax is used to provide protection against disease from infection with Haemophilus influen-zae type b (Hib), a bacterium, and hepatitis B virus (HBV).

Comvax provides 7.5 µg of Haemophilus b polysaccharide, 125 µg of Neisseria meningitidis OMPC, and 225 µg of alu-minum (as aluminum hydroxide) per 0.5 mL dose; plus 5 µg of recombinant hepatitis B virus surface antigen per standard 0.5 mL dose in 0.9% sodium chloride, with no preservatives, and with 25 µg of sodium borate decahydrate as a stabilizer. Comvax is available in single dose vials and as a box of five single dose vials. Comvax contain 1% or less yeast protein and no detectable yeast DNA (from the production of rHBsAg); and no more than 0.0004% residual formaldehyde. The vaccine is stored at 2-8˚C (refrigerated).

Nomenclature: Hib & Hepatitis B Vaccine, rDNA [BIO]; Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine [FDA]; hepatitis B virus surface antigen, recombinant, and Haemophilus influenzae type b (meningococcal protein conjugate) combination vaccine [SY]; HIB-HBV [CDC]

Companies.: This vaccine was developed and is manufactured by Merck & Co., Inc. (West Point, PA), FDA CBER est. no. 0002. It is marketed in the U.S. by Merck & Co., and internationally by Merck affiliates.

FDA class: Biologic PLA

CBER class: Bacterial Antigens and Vaccines

Approvals: Date = 19961002, first approval, PLA

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

COMVAX is indicated for vaccination against invasive disease caused by Haemophilus influenzae type b and against infection caused by all known subtypes of hepatitis B virus in infants 6 weeks to 15 months of age born of HBsAg negative mothers.

Status: Comvax was officially launched in the U.S. in March 1997.

COMVAX is not approved/used in European countries, and has not received centralized European Union approval.

Medical: Comvax is generally administered as a series of three injections at 2, 4, and 12 to 15 months of age. Infants from 2-14 months of age generally receive a primary course of vaccination with a standard 0.5 mL intramuscular dosage into the thigh at two months of age, and a second vaccination two months later (or as soon as possible after 2 months). Provided this regimen is completed by one year of age, a booster vaccination (0.5 mL) is generally administered at 12-15 months of age (generally, at least two months since the second primary dose). Comvax may be used to complete vaccination regimens started using monovalent Hib and hepatitis B virus vaccines. [See the product insert/labeling for further information].

The dosage of the Hepatitis B Vaccine (Recombinant) component in Comvax, a pediatric vaccine, is lower than that in the adult formulation of Recombivax HB; and is insufficient for use in adolescents, adults, and infants born to hepatitis B virus-infected (HBsAg-seropositive) mothers.

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 $43.56 (no change since 2005) for a package of 10 single dose vials, and $22.80 for 10-dose vials. The CDC Cost/Dose, the cost negotiated by NIP, CDC, for bulk contract purchase for public-sector state and local immunization programs, is $11.06 for 10-dose vials and packs of 10 prefilled 1-dose syringes ($10.82/dose in 2006; $10.42 in 2005). These prices include the $1.50/dose ($.75/covered component vaccine) Federal Excise Tax charged by the manufacturer for the federal vaccine injury compensation program. Merck’s contract with NIP, CDC, expires on March 31, 2008.

The 2007 Average Wholesale Price (AWP) is $540.71/10 single-dose vials, with a Direct Price (Manufacturer’s discount) of $435.57 (Red Book, 2007; unchanged since at least 2005).

In its March 22, 2006 price list, FFF Enterprises, a major biologics distributor, reported is price as $483.96/package of five single-dose vials plus diluent (no change from March 2005 or 2004).

Competition: Berna Biotech (Crucell N.V.) has developed Quinvaxem, a fully liquid pentavalent vaccine, combining DTaP with recombinant hepatitis B vaccine and a Haemophilus influenzae vaccine, produced by Crucell in Korea. Quinvaxem was co-developed with Chiron Corp., now Novartis Vaccines, which provides four of the five components as bulk. Quinvaxem received approval in South Korea in March 2007. Quinvaxem received World Health Organization (WHO) prequalification in Sept. 2006, and entered the international market in late 2006. The vaccine and its marketing are primarily oriented to lesser-developed countries. A total of 21.3 million doses were sold by Novartis in 2007, and 6.1 million doses in 2006. In Dec. 2006, Crucell received a $230 million, three-year supply contract from undisclosed “supranational organizations” (later identified as primarily UNICEF) for purchase of Quinvaxem and its Hepavax-Gene recombinant hepatitis B vaccine. At the time, Crucell reported, “ The total market potential is 150 million doses per year in 3 to 4 years.” Crucell has reported, "Most large countries where the UN organisation operates are now using Crucell's product and one reason they seem to be satisfied with Quinvaxem is that it does not need to be reconstituted before injection, saving much work."