Influenza A (H1N1) 2009 Monovalent Vaccine - influenza A/California/7/2009 (H1N1)v-like virus vaccine; monovalent pandemic (H1N1) 2009 influenza vaccine; swine flu vaccine
Status: supplemental BLA approved in Sept. 2009; acquired and distributed by the U.S. government and marketed for the 2009/10 flu season.
Organizations involved:
Sanofi Pasteur Inc. – Manuf; R&D; Tech.;World mark.
Sanofi Pasteur S.A. – Parent
Centers for Disease Control and Prevention (CDC) – USA mark. [to public health programs]
Cross ref.: See the entry for Fluzone, the seasonal trivalent vaccine of which this is an analog. See the entry for Panenza also from Sanofi Pasteur and similar to this vaccine, but developed for European markets. See also the Influenza H1N1 Vaccine Products and Influenza Vaccine Products entries.
Description: Influenza A (H1N1) 2009 Monovalent Vaccine from Sanofi Pasteur Inc is an aqueous split (purified surface antigen) subunit formulation of influenza A/California/7/2009 (H1N1)v-like virus cultured in embryonated hens’ eggs, inactivated with formaldehyde and disrupted (split) with polyethylene glycol p-isooctylphenyl ether (Triton X-100), with multi-dose vials preserved with thimerosal (mercury derivative; see related entry). This vaccine is substrantially similar to the company's Fluzone trivalent season vaccine and its Humenza European H1N1 nonadjuvanted vaccine (see related entries).
The vaccine (as approved by FDA) is formulated to contain 15 µg hemagglutinin (HA) of influenza A/California/07/2009 (H1N1)v-like virus per 0.5 mL dose. Gelatin (presumably of bovine or porcine origin) 0.05% is added as a stabilizer. Each 0.5 mL dose may contain residual amounts of formaldehyde (not more than 100 µg), polyethylene glycol p-isooctylphenyl ether (not more than 0.02%), and sucrose (not more than 2.0%). Antibiotics are not used in the manufacture of this vaccine. All presentations of Influenza A (H1N1) 2009 Monovalent Vaccine do not contain latex. The vaccine is stored at 2-8°C (35-6°F; refrigerated)
The vaccine is packaged in single-dose 0.5 mL prefilled syringes and 10-dose vials. Four presentations were approved:
1) Prefilled syringe, 0.25 mL, no preservative, for 6 through 35 months of age; distinguished by a pink syringe plunger rod;
2) Prefilled syringe, 0.5 mL, no preservative, for 36 months of age and older;
3) Single-dose vial, 0.5 mL, no preservative, for 36 months of age and older;
4) Multi-dose vial, 5 mL, for 6 months of age and older, contains thimerosal, a mercury derivative, added as as an antimicrobial preservative. Each 0.5 mL dose contains 25 µg (mcg) mercury.
Companies.: The vaccine was developed and is manufactured by Sanofi Pasteur Inc., CBER/FDA est. no. 1715, in Swiftwater, PA.
Production of the new A(H1N1) vaccine for HHS takes place initially in Sanofi Pasteur's new influenza vaccine production facility in Swiftwater. Once ongoing seasonal influenza production concludes at its second older facility in Swiftwater, A(H1N1) or other pandemic influenza vaccine production can occur in both facilities. FDA approved the facility for manufacture of egg cultured influenza vaccines in May 2009. The $150 million, 140,000 square-foot facility incorporates the latest technology in egg-based vaccine production. When operating at full capacity, the new influenza facility is expected to produce 100 million doses of trivalent seasonal influenza vaccine annually, and presumably an equivalent 300 million doses of monovalent vaccine. In total, Sanofi Pasteur has a U.S.-based capacity of for 150 million doses of trivalent seasonal vaccine per year (or 450 million monovalent doses) – 50 million doses from the existing facility and 100 million doses from the new facility.
In May 2009, BARDA/NIAID, NIH, HHS (federal government) placed a $190 million order for the production of bulk vaccine and related activities. In Sept. 2009, HHS placed an additional order for bulk antigen equivalent to 27.3 million doses based on 15 µg of antigen per dose. This contract was likely for $20 million or more. Delivery of vaccine began on Sept. 29.
Separate from actual vaccine purchases, in June 2007, Sanofi Pasteur received a $77.4 million contract BARDA/NIAID, NIH, HHS (federal government) to retrofit its existing influenza vaccine manufacturing facility, to enable the company to switch to pandemic influenza vaccine manufacture at the HHS' request. The contract covers costs for design, retrofit and the maintenance of the facilities at a state of readiness so the company can switch to pandemic influenza vaccine manufacture at the HHS' request. Sanofi pasteur will contribute ~$25 million to the overall project. This was company’s seventh pandemic influenza-related contract with the U.S. government, with this including H5N1 vaccines. Previous contracts covered the production of investigational doses for clinical trials; bulk H5N1 vaccine for stockpiling; the establishment and maintenance of laying chicken flocks to enable year-round egg production (not just seasonal); as well as a contract to speed the production process for new cell culture influenza vaccines, including the design of a U.S.-based cell-culture vaccine manufacturing facility.
GSK reports having spent more than $3.2 billion on research, acquisitions and extra manufacturing in anticipation of an influenza pandemic (in 2009-2010). This includes acquisition of ID Medical, and doubling manufacturing capacity at its plant in Germany (both of which are more relevant to seasonal vaccines). Also, GSK donated 50 million doses of Panenza to the World Health Organization for use in poor countries.
Manufacture: Sanofi Pasteur’s Influenza A (H1N1) 2009 Monovalent Vaccine and its seasonal trivalent Influenza Virus Vaccine (Fluzone) are manufactured using substantially the same process.
The vaccine is prepared from influenza viruses propagated in embryonated specific pathogen-free (SPF) chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Influenza virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, polyethylene glycol p-isooctylphenyl ether (Triton® X-100), producing a “split virus”. The split virus is further purified and then suspended in sodium phosphate-buffered isotonic sodium chloride solution.
Thimerosal is not used in the manufacturing process of the single-dose presentations. The multi-dose presentation contains thimerosal, a mercury derivative, (see related entry) added as an antimicrobial preservative.
FDA class: Biologic BLA
Approvals: Date = 20090915; sBLA (BL 103914/5260), referencing the 1980 original Fluzone seasonal vaccine approval
Indications: [Full text of the "Indications and USAGE" section of product insert/labeling];
Influenza A (H1N1) 2009 Monovalent Vaccine is an inactivated influenza virus vaccine indicated for active immunization of persons 6 months of age and older against influenza disease caused by pandemic (H1N1) 2009 virus.
Status: On Sept. 15, 2009, FDA granted this H1N1 vaccine (and 3 others) supplemental BLA approval, based on the presumption that the vaccine is substantially similar, including manufacturing process and specifications, to the comparable Sanofi Pasteur seasonal vaccine, Fluzone, except for being monovalent and using an H1N1 strain.
Trials: In Sept., NIAID reported most children over 10 need only one H1N1 vaccine dose. A single inoculation is enough to produce immunity in 76% of children over the age of 10. However, "only 25 percent of babies age six months to 35 months, and 36 percent of kids ages three to nine, had a strong response" to a single dose, "indicating that they will need two shots." Overall, this was very good news for the U.S. vaccination program.Young children (<10 years old) who has never received a seasonal flu vaccine will need four shots total: two seasonal flu shots and two swine flu shots.
In Oct, 2009, Sanofi Pasteur reported that a single dose of Panenza (15 µg dose, non-adjuvanted), which is similar to this U.S. vaccine, administered to children (3 years of age and older) and adults induced a robust immune response (HA seroprotective antibody titers) that is considered protective. This included 93% or more of adults 60 years of age and older. In children 3 years of age through 17 years of age, 94%t or more of study participants achieved seroprotective antibody response. An antibody titer of 1:40 or greater is generally considered a marker of seroprotection. The results indicate that only a single dose is required.
Market: As discussed in the Status section, in 2009 GSK sold $200 million or more in bulk vaccine to the U.S. government. Crudely presuming a comparable level of orders outside of the U.S. for finished and bulk vaccine, GSK's total 2009 (2009/10 flu season) sales are likely about $400 million. Thus, total revenues for CAIV-T H1N1 of about $800 million are estimated to be about the same as for the comparable FluMist seasonal vaccine's sales.
Ongoing: In July 2009, Glaxo announced a deal with Enigma Diagnostics (U.K.)to develop an automated device that would diagnose (identify and type) influenza viruses from swab samples in 60 minutes or less.
Companies involvement:
Full monograph
483.4 Influenza vaccine, H1N1/Sanofi
Nomenclature:
Influenza vaccine, H1N1/Sanofi [BIO]
Influenza A (H1N1) 2009 Monovalent Vaccine [FDA]
H1N1 2009 influenza vaccine [SY]
swine flu vaccine [SY]
NDC 49281-650-25; NDC 49281-650-70; NDC 49281-650-50; NDC 49281-650-90; NDC 49281-650-10; NDC 49281-640-15 [NDC]
FDA Class: sBLA
Year of approval (FDA) = 2009
Date of 1st FDA approval = 20090915
(in format YYYYMMDD)
Index Terms:
chicken source materials
nonoxynol 101 (Triton N101)
vaccines, inactivated
vaccines, subunit
vaccines, viral
chicken embryo (egg) culture
infertility treatment
gelatin (bovine source)
hemagglutinin (HA) antigen, influenza A virus
polyethylene glycol (PEG)
sodium chloride
sodium phosphate
sucrose
thimerosal (mercury derivative)
virus culture
EU000 Not yet/Never filed with EU
UM100 Controlled/Gov't Distribution in US
US200 Currently Approved in US
EM999 Not Available/Not Marketed in EU
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