Rubella Virus Vaccine Live - Meruvax II
Status: withdrawn from U.S. market in 2011
Organizations involved:
Merck & Co., Inc. – Manuf.; R&D; Tech.; USA mark.; Intl. mark.
Sanofi Pasteur MSD – Europe mark.
Wistar Institute – R&D; Tech.
Div. of Biologics Standards, NIH – R&D; Tech.
Walter Reed Army Inst. of Research – R&D; Tech
Childrens Hospital – R&D
Cross ref: See the entry for Measles, Mumps and Rubella Virus Vaccine Live (M-M-R II) (#493) from Merck including this vaccine as a component.
Description: Rubella Virus Vaccine Live or Meruvax II is a lyophilized (freeze-dried) formulation of live attenuated rubella virus (Wistar Institute RA 27/3 strain) for vaccination against rubella (German measles). The virus is cultured in WI-38 human diploid lung fibroblasts using Minimum Essential Medium (MEM; buffered salt solution containing vitamins and amino acids and supplemented with fetal bovine serum) also containing Albumin (Human) and the antibiotic neomycin. Sor-bitol and hydrolyzed gelatin (bovine source) are added as stabilizers to the virus harvests. The cells, virus pools, fetal bovine serum, gelatin, and human albumin are all screened for the absence of adventitious agents.
The vaccine is supplied in single-dose vials along with diluent for subcutaneous administration. Each 0.5 mL dose contains over 1,000 TCID50 (tissue culture infectious doses50) of rubella virus. Each dose also contains sorbitol (14.5 mg), sodium phosphate, sucrose (1.9 mg), sodium chloride, hydrolyzed gelatin (14.5 mg), human albumin (0.3 mg), fetal bovine serum (<1 ppm), other buffer and media ingredients, and approximately 25 µg of neo-mycin. The product contains no preservatives. The vaccine is stored at 2-8°C (36-46°F; refrigerated) or colder. The vaccine must be maintained at a temperature of 10°C (50°F) or colder during shipment to ensure no loss of potency. Freezing during shipment does not affect potency. Exposure to light may inactivate the virus.
Nomenclature: Rubella Virus Vaccine [BIO]; MERUVAX II [TR]; Rubella Virus Vaccine Live [FDA USAN]; MERU-VAX [TR; former for 1st generation vaccine]; German measles vaccine [SY]; NDC 0006-4747-00; NDC 0006-4673-00; NDC 0006-4674-00; NDC 0006-4747-00; NDC 0006-4673-00; NDC 0006-4675-00 [NDC]
History: Drs. Parkman, Buescher, and Artenstein at Walter Reed Army Institute of Research (WRAIR), U.S. Army, collaborating with Dr. T. Weller, Harvard School of Public Health, isolated rubella virus in 1961. Merck investigators isolated the Benoit strain of rubella virus in 1962. However, the virus would not grow in available media/hosts, e.g., chick-embryo cell culture. In the mid-1960s, competing groups, including Merck and Drs. Meyer, Parkman, et al., Div. of Biologics Standards (DBS; later became CBER, FDA), NIH, developed live vaccines propagated in different host cells. Merck further attenuated the DBS’ strain HPV-77 of rubella virus using bovine kidney cells and attenuation by 77 passages in duck embryo (egg) cell culture. Merck developed and maintained its own flocks of disease-free Peking ducks for production of fertilized eggs as a source for cells for culture.
The original, first generation, duck embryo cell cultured Meruvax vaccine using the NIH DBS HPV-77 rubella virus strain was highly reactogenic (fevers, rashes, arthritis, arthralgia) in about 60% of adult women, but had no serious reacto-genicity in children under age 12. The U.S. Public Health Service implemented policies supporting pediatric vaccination, designed to indirectly prevent adult exposure. Of 13 million children vaccinated by 1972, 11 million received vaccine from public health programs.
The WI-38 host cell line used for culturing the virus for Meruvax II was developed by Drs. L. Hayflick and P.S. Moorehead, Wistar Institute. Dr. S. Plotkin, Wistar Institute, and collaborators developed the Wistar Institute RA 27/3 strain of rubella virus used for Meruvax II.
Companies previously licensed for manufacture of Rubella Virus Vaccine Live included Dow Chemical Co. (March 1974-June 1978); Smith Kline–RIT S.A. (March 1970-Oct. 1982); and Wellcome Foundation Ltd. (March 1977-Feb. 1994). Phillips Roxane Labs., Inc. (Columbus, OH) received FDA approval for a live rubella vaccine only about 6 months after approval of the original Merck vaccine. However, CBER/FDA official approval lists no longer include this vaccine.
Companies.: Meruvax II is manufactured by Merck & Co., Inc. (West Point, PA), CBER/FDA lic. no. 0002. It is marketed in the U.S. by Merck & Co., and internationally by Merck & Co. affiliates. The vaccine is marketed in Europe by Sanofi Pasteur MSD, a joint venture of Sanofi Pasteur S.A. and Merck.
In 2006, a new vaccine manufacturing facility in Durham, NC, came came online, with completion/approval expected in 2010. M-M-R II, its component vaccines and Zostavax are manufactured there..
FDA class: Biologic PLA
CBER class: Viral And Rickettsial Vaccines
Approvals: Date = 19690609; PLA; for Meruvax
Date = 19790000; supplemental PLA; for Meruvax II using Wistar Institute RA 27/3 strain and WI-38 cell culture
Indications: [portion of the "INDICATIONS AND USAGE” section of the product insert/labeling]:
Recommended Vaccination Schedule: MERUVAX II is indicated for vaccination against rubella in persons 12 months of age or older. It is not recommended for infants younger than 12 months because they may retain maternal rubella neutralizing antibodies that may interfere with the immune response. Children in kindergarten and the first grades of elementary school deserve priority for vaccination because often they are epidemiologically the major source of virus dissemination in the community.
Status: The Code of Federal Regulations (CFR), Subpart G, Sec. 630.60, “Rubella Virus Vaccine Live,” describes rubella vaccines, requirements for their approval, and other aspects including the monkey neuro-virulence test used to test the pathogenicity (encephalitis or brain-infecting capability) of each lot of manufactured virus.
According to FDA, “Products that are manufactured in genetically unmodified MRC-5 or WI-38 cells do not need characterization of these cell substrates by karyology or tumorigenicity since extensive characterization has already been performed and published for these cell lines.”
On May 24, 2011, FDA approval was withdrawn and the product "discontinued."
Disease: Rubella, whose name means “little red,” was originally thought to be a variant of measles until 1814, when German researchers described it as a distinct illness. Rubella causes a short-lived red rash, low-grade fever and, in adult women, often pain in the joints. Infection is generally mild and often entirely unnoticed in children. Howver, women infected with the virus in the first three months of pregnancy generally experience a miscarriage, or deliver a stillborn or permanently disabled child. In the last great U.S. epidemic of rubella, ~40 years ago (before the vaccine), about 12,000 babies were born deaf or deaf and blind. In pregnant women, the virus crosses the placenta and infects the fetus 50-85 percent of the time, causing cells of the fetus to die or stop dividing.
Because of widespread vaccination in the U.S., cases of rubella have steadily declined since the introduction of Meruvax in 1969. That year, nearly 60,000 cases of rubella were reported. By 1972, reported cases dropped by more than half to 25,501 cases. By 1979, only 12,000 cases were reported, and by 2002, only 18 cases were reported. Fewer than 10 people a year in the U.S. now contract rubella. Worldwide, approximately half of all countries have rubella vaccination programs. Outside the U.S., approximately 100,000 cases of Congenital Rubella Syndrome are reported each year.
In March 2005, the Centers for Disease Control and Prevention (CDC) announced that rubella “is no longer a health threat in the United States.” Thus, rubella in the U.S. has been “eliminated,” meaning the disease is no longer endemic, with all new cases arising from foreign countries. “Eradicated” means there are no cases from any source. Global eradication of rubella, while conceivable, is a distant goal. Rubella vaccine is not yet part of the standard package of childhood immunizations in many developing countries. The annual number of cases globally is unknown. The World Health Organization (WHO) estimates that 100,000 babies are born with “congenital rubella syndrome” a range of birth defects caused by rubella infection of pregnant women.
In the Sept. 2008 issue of the American Journal of Ophthalmology, it was reported that childhood vaccination for the rubella virus may have also almost entirely eliminated an inflammatory eye disease, Fuchs heterochromic iridocyclitis, from the U.S.-born population.
Trials: Extensive clinical trials involving 28,000 subjects were conducted with the rubella strain used in Meruvax II. A single injection produces rubella-inhibiting antibodies in more than 97% of susceptible persons. Protective antibody levels generally persisted for at least 10 years. The rubella virus strain used in Meruvax II produces higher and broader profile antibody responses, and stimulates natural infection more closely than strains used in most other rubella vaccines worldwide.
Medical: A single 0.5 mL dose is administered subcutaneously. This live virus vaccine produces a modified, noncommunicable rubella infection, possibly including rash, sore throat, fever, headache, dizziness, nausea, vomiting, diarrhea, runny nose, mild regional lymphadenopathy, joint pain, and/or transient arthritis. Fever is rarely greater than 103˚F.
Market: With its withdrawal from the U.S. market, the Advisory Committee on Immunization Practices (ACIP) recommended the use of combined measles-mumps-rubella vaccine (M-M-R® II - Measles, Mumps, and Rubella Virus Vaccine Live) for appropriate individuals to help protect against measles, mumps, and rubella.
The 2007 Average Wholesale Price (AWP) is $219.82/10 single dose vials, with a Direct Price (Manufacturer’s discount price) of $184.43 (Red Book, 2007). All Meruvax II prices include $.75/dose federal excise tax charged by the manufacturer used to fund federal vaccine liability insurance.
The National Immunization Program, Centers for Disease Control and Prevention (CDC), now uses multivalent vaccines, M-M-R II and ProQuad, rather than monovalent Meruvax for public health/vaccination programs. NIP, CDC, had purchased the vaccine in bulk for $6.30/dose (contract ending 3/31/01).
In Nov. 2004, the Centers for Disease Control and Prevention (CDC) reported that rubella vaccine coverage (the percentage of those vaccinated) among U.S. children entering school (kindergarten) in 2003-2004 was 95.9%.
Competition: The vaccine has no competition in the U.S. market. Most measles vaccinations in the U.S. involves use of the triple combination Measles, Mumps and Rubella Virus Vaccine Live (M-M-R II) and newer ProQuad, rather than monovalent Meruvax II.
Companies involvement:
Full monograph
533 Rubella Virus Vaccine
Nomenclature:
Rubella Virus Vaccine [BIO]
MERUVAX II [TR]
Rubella Virus Vaccine Live [FDA USAN]
Rubella Virus Vaccine Live USP [USP]
MERUVAX [TR; formrer, for 1st generation vaccine]
German measles vaccine [SY]
NDC 0006-4747-00; NDC 0006-4673-00; NDC 0006-4674-00; NDC 0006-4747-00; NDC 0006-4673-00; NDC 0006-4675-00 [NDC]
FDA Class: Biologic PLA
Year of approval (FDA) = 1969
Date of 1st FDA approval = 19690609
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
bovine materials used<!-- bovinesource -->
human materials used<!-- humansource -->
live microorganisms (as active agent)
vaccines, live
vaccines, viral
bovine serum
cells, human
fibroblasts, WI-38 human diploid
mammalian cell culture
Minimum Essential Medium (MEM)
RA 27/3 Wistar Inst. strain, rubella virus
rubella virus Wistar Inst. RA 27/3 strain
virus culture
WI-38 human diploid fibroblasts
Albumin (Human)
gelatin (bovine source)
lyophilized (freeze-dried)
neomycin
sodium chloride
sodium phosphate
sorbitol
sucrose
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)
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
Copyright© 2020, Biotechnology Information Institute