Status: supplemental BLA approved in Sept. 2009; acquired by the U.S. government for the 2009/10 flu season

Organizations involved:

CSL Ltd. – Manuf; R&D; Tech.;World mark.

CSL Biotherapies Inc. – USA mark.; Manuf. other

Centers for Disease Control and Prevention (CDC)– USA mark. [`to public health programs]

Cross ref.: See the entry for Afluria, the seasonal vaccine from CSL of which this is an analog using a seasonal strains (although there are differences, such as inactivation agents). See the Influenza H1N1 Vaccine Products and Influenza Vaccine Products entries.

Description: Influenza A (H1N1) 2009 Monovalent Vaccine from CSL is a monovalent influenza H1N1 split virion vaccine containing inactivated influenza virus conventionally cultured in the allantoic fluid of embryonated chicken eggs, inactivated with beta-propriolactone (BPL), and disrupted with the virus particles are disrupted using sodium taurodeoxycholate (detergent). Influenza A (H1N1) 2009 Monovalent Vaccine from CSL is much the same as the company's seasonal vaccine, Afluria, except using a different influeza virus strain, A/California/07/2009 (H1N1)v. Following harvest, the virus is purified in a sucrose density gradient using a continuous flow zonal centrifuge. The purified virus is inactivated with beta-propiolactone, and the virus particles are disrupted using sodium taurodeoxycholate to produce a “split virion” vaccine. The disrupted virus coat surface proteins (HAand NA) are further purified and suspended in a phosphate buffered isotonic solution.

Influenza A (H1N1) 2009 Monovalent Vaccine is formulated to contain 15 mcg HA per 0.5 mL dose of influenza A/California/7/2009 (H1N1)v-like virus.

Influenza A (H1N1) 2009 Monovalent Vaccine is supplied in two presentations: 0.5 mL preservative-free, single-dose, pre-filled syringes; and 5 mL multi-dose vials containing ten doses. The single-dose formulation is preservative-free. The multi-dose formulation contains thimerosal (mercury derivative; see related entry) added as an antimicrobial preservative, with each 0.5 mL dose containing 24.5 µg of mercury. The vaccine is stored at 28°C (3646°F; refrigerated).

Each 0.5 mL dose of Influenza A (H1N1) 2009 Monovalent Vaccine contains sodium chloride (4.1 mg), monobasic sodium phosphate (80 µg), dibasic sodium phosphate (300 µg), monobasic potassium phosphate (20 µg), potassium chloride (20 µg), and calcium chloride (1.5 µg). From the manufacturing process, each dose may also contain residual amounts of sodium taurodeoxycholate (≤ 10 ppm), ovalbumin (≤ 1 mcg), neomycin sulfate (≤ 0.2 picograms [pg]), polymyxin B (≤ 0.03 pg), and beta-propiolactone (< 25 nanograms). The vaccine may also contain traces of egg and chicken proteins.

Nomenclature: Influenza vaccine, H1N1/CSL [BIO]; influenza A (H1N1) 2009 Monovalent Vaccine [FDA]; H1N1 2009 influenza vaccine [SY]; swine flu vaccine [SY]; H1N1 2009 influenza vaccine [SY]; NDC 33332-519-01; NDC 33332-629-10 [NDC]

Companies.: The vaccine was developed and is manufactured by CSL Ltd., Melbourne, Australia.

In 2009, CSL received a contract from BARDA, NIAID, NIH, HHS for $180 million worth of bulk influenza A/California/7/2009 (H1N1)v antigen for formulation and packaging into finished vaccine, if needed. CSL Biotherapies negotiated an option to supply HHS with A (H1N1) antigen filling and finishing services at the company’s manufacturing plants in Kankakee, IL, and in Marburg, Germany. CSL also received a contract to supply 21 million doses of finished swine flu vaccine to the Australian government.

CSL Ltd. has made a $60 million investment in plant and equipment to double the manufacturing capacity of the company’s Melbourne facility to 40 million doses per season.

FDA class: Biologic BLA

Approvals: Date = 20090915; sBLA (BL 125254/127); Note, this was a supplemental, not full/original, BLA approval,

Indications: [full text of the "Indications and USAGE" section of the product insert/labeling]:

Influenza A (H1N1) 2009 Monovalent Vaccine is an inactivated influenza virus vaccine indicated for active immunization of persons ages 18 years of age and older against influenza disease caused by pandemic (H1N1) 2009 virus.

This indication is based on the immune response elicited by the seasonal trivalent Influenza Virus Vaccine manufactured by CSL (AFLURIA). CSL’s Influenza A (H1N1) 2009 Monovalent Vaccine and AFLURIA are manufactured by the same process. There have been no controlled clinical studies demonstrating a decrease in influenza disease after vaccination with AFLURIA (see Clinical Studies).

Status: On Sept. 15, 2009, FDA granted this (and 3 other) H1N1 vaccines receive supplemental BLA approval, based on the presumption that the vaccine is substantially similar, including manufacturing process and specification, to the seasons Aflluria vaccine, except for being monovalent and using an H1N1 strain.

Trials: CSL conducted a Phase II study involving 240 subjects aged 18 to 64 years. Subjects who were pregnant or who may have had prior exposure to the novel virus were excluded. Subjects were inoculated with either a 15- or a 30-µg dose. A single dose of the vaccine produced sufficient titers (hemagglutinin-inhibition assay titers [HAI] of 1:40 or greater) in 96.7% of the subjects who received the 15 µg version and in 93.3% who received the 30µg injection. There were no serious adverse events reported, and fewer than half of the subjects complained of local adverse events (e.g., injection site tenderness) or systemic adverse events (e.g., headache, malaise, etc). It was also observed taht 31.7% of subjects had baseline antibody titers of 1:40 or more to the novel virus; 44.4% of those who had received the 2009 seasonal vaccine (Southern Hemisphere version) had titers of 1:40 or more to the novel virus, while only 21.2% of those that did not receive the seasonal vaccine had similar levels of titers; and subjects over age 50 had less robust responses to the vaccine than did those in younger age cohorts.

Medical: Adults 18 years of age and older should receive a single 0.5 mL intramuscular dose. The preferred site for intramuscular injection is the deltoid muscle of the upper arm.

Market: As of Oct. 15, 2009, FDA reported zero lots of CSL's H1N1 vaccine having received lot release approval, indicating that this vaccine was not being distributed in the U.S., including both sales by CSL and finished vaccine purchased by the federal government.

The author very crudely estimates total 2009 (2009/10 flu season) sales of $400-500 million, with about half of this in the U.S., including the major government purchases. As with most H1N1 vaccines, most doses being manufactured are being purchased by governments worldwide, generally at around $10/dose.

Analysts have predicted that CSL's eventual 2009 profits from sales of H1N1 vaccine and ingredients will be between $218-$262 million.