Status: launched in U.S. in 2006; marketed in Canada

Organizations involved:

ID Biomedical Corp. – Manuf.; R&D; Tech.

GlaxoSmithKline Inc. (GSK) –USA mark.

GlaxoSmithKline plc (GSK) – Parent

AmerisourceBergen Corp. – USA mark.

Shire Biologics, Inc. – Former

Shire Pharmaceutical Group plc – Parent; Former

BioChem Pharma Inc. – Former

IAF BioChem Intl. Inc. – R&D; Tech.; Former

Cross ref.: See the Influenza Vaccine Products entry.

Description: FluLaval, also widely known as Fluviral, is a conventional aqueous trivalent inactivated split influenza virus vaccine. Like other influenza vaccines, the product is manufactured from three selected strains of influenza viruses types A and B cultured in the allantoic cavity of embryonated fertile chicken embyros (eggs). Each of the influenza virus strains is cultured and purified separately. The virus is inactivated with ultraviolet light treatment, followed by formaldehyde treatment, purification by centrifugation, and further virus inactivation with sodium deoxycholate.

FluLaval is available as 5-mL multi-dose vials containing 10 doses. Each 0.5 mL dose contains a total of 45µg hemagglutinin from the three influenza virus types in the vaccine. FluLaval/Fluviral contains traces of formaldehyde (from inactivation), sodium deoxycholate, and 0.01% thimerosal (mercury-based antimicrobial preservative; see related entry). Each dose contains 25 µg mercury. Each dose may also contain residual amounts of egg proteins (≤1 µg ovalbumin), formaldehyde (≤25 µg), and sodium deoxycholate (≤50 µg). Antibiotics are not used in the manufacture of this vaccine.

Nomenclature: Influenza vaccine/GSK Canada [BIO]; Influenza Virus Vaccine, Trivalent [FDA]; FluLaval [TR]; Fluviral [TR in Canada]; NDC 19515-883-07 [NDC]

Companies.: GlaxoSmithKline plc (GSK) now manufactures and markets FluLaval/Fluviral.

The vaccine was originally developed by IAF BioChem Intl. Inc., which became BioChem Pharma Inc.,, which was acquired by Shire Pharmaceutical Group plc in late 2000. ID Biomedical completed its acquisition of the vaccines business of Shire in Sept. 2004. GSK acquired ID Biomedical in Dec. 2005, and GlaxoSmithKline Inc. markets the product in the U.S. as FluLaval.

FluLaval/Fluviral is manufactured by ID Biomedical Corp. (GSK), CBER/FDA est. no. 1739. ID Biomedical/GSK manufactures FluLaval/Fluviral at two facilities located in Laval and Quebec City, both in Quebec province. The Quebec City facility is being expanded to increase total manufacturing capacity to ~50 million doses by 2007, and will house what is believed to be the newest egg-based vaccine production facility in the world.

In 2001, Shire (now ID Biomedical/GSK) signed a ~$223 million contract to supply Fluviral to the Canadian government for the next seven years. For the 2004/2005 flu season, ID Biomedical provided the Canadian government with 7-8 million doses, and manufactured another 500,000 for Canadian private sector sales (primarily to physicians/clinics to vaccinate people who fall outside the priority groups covered by the national health plan, and to companies that offer it to their employees). [Note, Sanofi Pasteur Ltd. is the only other Canadian manufacturer of influenza vaccine. For the 2004/5 flu season, the two companies together manufactured a total of 9.7 million doses for Canadian use].

FDA class: Biologic BLA

Approvals: Date = 20061005; original BLA

Indications: [full text of the "INDICATIONS AND USAGE” section of product insert/labeling upon approval]

FluLaval is indicated for active immunization of adults (18 years of age and older) against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine (see DOSAGE FORMS AND STRENGTHS [3]).

This indication is based on immune response elicited by FluLaval, and there have been no controlled trials demonstrating a decrease in influenza disease after vaccination with FluLaval (see CLINICAL STUDIES [14]).

FluLaval is not indicated for use in children.

Status: A BLA for Fluviral was approved in Aug. 31, 2005. The BLA was submitted with fast track designation, which allowed submission and review of sections of the BLA as they were completed. Fluviral was granted accelerated approval and priority review.

FluLaval was approved using FDA’s accelerated approval pathway, which allows the agency to approve products for serious or life-threatening diseases based on early evidence of a product’s effectiveness, reducing the time it takes for needed medical products to become available to the public. In this case, GSK demonstrated that the vaccine induced levels of antibodies in the blood likely to be effective in preventing seasonal influenza. As part of the accelerated approval process, GSK will conduct further studies to verify that the vaccine will decrease seasonal influenza disease after vaccination.

In many respects, FluLaval’s FDA approval may be considered to be a biogeneric, follow-on biologic, biosimilar, or other generic approval, since it was based on an abbreviated filing involving comparative clinical testing, rather than full placebo-controlled Phase III-like testing.

GSK expected to manufacture and supply 30 million doses of influenza vaccine (FluLaval and Fluarix) for the 2006/7 U.S. flu season, with supplies increasing in coming years. Approval was received in time for marketing of the vaccine for the 2006/7 flu season.

Fluviral has long been approved in Canada, where it is the primary influenza virus vaccine. The primary purchasers are the federal and provincial governments. In addition to Canada, the vaccine is licensed in Argentina, Mexico, the Philippines, Romania, China and Taiwan.

Trials: In March 2005, with the filing of its pivotal BLA, ID Biomedical completed enrollment of 1,000 healthy adults in the U.S. double-blind Phase III trials of FluLaval comparing it to several other available influenza vaccines. Other data from use of the vaccine in Canada, where Fluviral has been available since 2001, were also evaluated as part of FDA’s safety assessment. After vaccination, the rate and nature of side effects with FluLaval were similar to those seen with other licensed seasonal influenza vaccines.

R&D: ID Biomedical (now GSK) had been developing an intranasal influenza vaccine, FluINsure, and a cell culture-based influenza vaccine manufactured vaccine. In Sept. 2004, the company received a $9.5 million grant from the National Institutes of Health (NIH) to fund further development and early-stage trials with the cell cultured vaccine.

GSK is developing a new cell culture-based infleunza vaccine formulation with a novel adjuvant system, expected to substantially increase and support approvals for use in person over age 65. The adjuvant is designed to restore T-cell responses after vaccination to levels seen in younger people and to enhance protection against drift influenza strains. In early trials in 360 elderly subjects, the vaccine was as well tolerated as Fluarix, and increased influenza virus-specific T-cell responses by ~60%. A pivotal trial in 3,500 patients in Europe and the U.S. began in fall 2006.