Hepatitis B Vaccine Inactivated - Heptavax-B
Status: formerly approved
Organizations involved:
Merck & Co., Inc. – Manuf.; R&D; Tech.; World mark.; Former
Cross ref: See Hepatitis B Vaccine Products (#458).
Description: Hepatitis B Vaccine Inactivated or Heptavax-B (no longer U.S. approved or marketed) contained hepatitis B virus surface (s) antigen (HBsAg) particles isolated from the pooled blood of hepatitis B virus-infected (HBsAg-seropositive) donors. These negatively charged particles were com-plexed with sodium ions to form a salt, and the vaccine was subjected to multiple viral inactivation steps including formaldehyde and heat treatment (pasteurization).
Heptavax-B was the first hepatitis B virus vaccine and the first viral subunit vaccine approved in the U.S. in 1981. The vaccine was replaced by recombinant HBsAg vaccines.
The Heptavax-B manufacturing process was complex and required 65 weeks, the longest production time for any vaccine at the time. The HBsAg was a highly purified product. The combination of isopycnic banding and rate zonal purification steps resulted in about a 2,000-fold purification of HBsAg relative to normal plasma protein.
Nomenclature: Hep. B Vaccine, blood-derived [BIO]; Hepatavax-B [TR]; Hepatitis B Vaccine Inactivated [FDA]; HBV [CDC]
History: Initial clinical trials were performed among Merck employees and their families (something not done now). Further clinical trials began in 1978 in a high risk group, homosexuals in New York City, conducted by Szmuness, et al. Other pivotal clinical trials also concentrated on enrolling male homosexuals.
Some observers, notably some with beliefs or political agendas highly critical of homosexuality, now refer to the vaccine as having been developed primarily for male homosexuals. With blood-borne and sexually-transmitted HBV infection then at epidemic rates (much as it would later be with similarly transmitted HIV-infection), this was an obvious group in which to conduct trials. There have also been allegations linking the vaccine’s testing and use in homosexuals as contributing to or even causing the HIV epidemic in the U.S. Heptavax-B’s testing and use in male homosexuals occurred just about when the HIV epidemic likely started in the U.S., (in much the same groups in the same major cities as participants in the vaccine’s clinical trials and its early users). See studies, e.g., Szmuness W., et al., Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States, N Engl J Med 1980 Oct 9;303(15): 833-41; and Francis D.P., et al., The prevention of hepatitis B with vaccine. Report of the Centers for Disease Control multi-center efficacy trial among homosexual men., Ann. Intern. Med., 1982 Sep. 97(3):362-6.
Over 1.5 million people received Heptavax-B. Vaccine supply problems and cost, linked to its complex manufacturing process, restricted its wider use. At the time, Heptavax-B was the most expensive vaccine, costing over $100 for a course of three inoculations.
AIDS (the disease, not HIV) was first recognized in 1981, the same year Heptavax-B was launched, and there were concerns that the vaccine might be spreading the disease, particularly among male homosexuals, a group with a high incidence of AIDS. After discovery of the HIV virus in 1983, it was demonstrated that the Heptavax-B manufacturing process fully inactivated detectable HIV. However, concerns over use of a vaccine derived from hepatitis B virus-infected carriers decreased its use, e.g., some insurance companies refused to pay for the vaccine.
Despite being isolated from blood containing infectious hepatitis B virus, the vaccine was never associated with any cases of infection. Similar blood-derived, inactivated HBsAg vaccines are still used internationally with no known increased risks for HIV (or hepatitis B virus) infection.
Companies.: Heptavax-B was developed and manufactured by Merck & Co. (West Point, PA), FDA CBER est. no. 0002. It was marketed in the U.S. by Merck, and internationally by Merck affiliates.
FDA class: Biologic PLA
CBER class: Blood and Blood Derivatives
Approvals: Date = 19811116; first approval, PLA
Date = 19950315; license revoked voluntarily
Indications: for immunization of persons, particularly in high-risk groups, two years of age and older against disease caused by hepatitis B virus
Status: Besides the U.S., the vaccine is presumed to also have been approved and marketed in European and other countries worldwide.
Medical: The Heptavax-B vaccine regimen was much the same as for current recombinant vaccines – a 10 µg HBsAg dose was administered at months 0, 1 and 6. An alternative 2-dose adolescent regimen at and 2-4 months was also used.
Companies involvement:
Full monograph
469 Hepatitis B Vaccine, blood-derived
Nomenclature:
Hepatitis B Vaccine, blood-derived [BIO]
Hepatavax-B [TR]
Hepatitis B Vaccine Inactivated [FDA]
FDA Class: Biologic PLA
Year of approval (FDA) = 1981
Date of 1st FDA approval = 19811116
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
blood products
human materials used<!-- humansource -->
vaccines, inactivated
vaccines, viral
hepatitis B virus (HBV)
formaldehyde
heat treatment (pasteurization)
Plasma (Human)
sodium bromide
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)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
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North American coral snake
EU011 Approved Formerly in EU/withdrawn
UM999 Not Available/Not Marketed in US
US011 Approved Formerly in US/withdrawn
EM999 Not Available/Not Marketed in EU
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