1. Vaccines and Related Biological Products Advisory Committee 18 February 2009 Topic 2: Considerations and Implications for adding two B Strains to the Seasonal Influenza Vaccine Rakesh Pandey, Ph.D. Division of Vaccines and Related Products Applications/OVRR/CBER/FDA

2. 2 INTRODUCTION 2007 VRBPAC discussed the challenges with regard to the two co-circulating antigenically distinct lineages of influenza B viruses, B/Yamagata and B/Victoria –Is there a public health need for inclusion of a second influenza B strain in the seasonal vaccine ? –What is the public health impact of mismatches of the B strain in the vaccine ? –What is the regulatory pathway for developing and licensing a quadrivalent influenza vaccine ? Manufacturing capacity Clinical requirements for safety and efficacy

3. 3 Influenza B viruses do not have subtypes Current trivalent seasonal influenza vaccines contain a single B component There is limited information on the effectiveness of the B component in the vaccine –Relatively small number of studies have evaluated efficacy in general –In these studies, the limited B circulation did not allow a reliable calculation of effectiveness specific for the circulating strains Background

4. 4 Antigenic composition of influenza vaccines may change yearly Influenza vaccine is the only vaccine for which annual recommendations are made for composition of the vaccine All manufacturers generate vaccine with the same influenza strain composition It is the only vaccine for which reagents for standardization are prepared and distributed yearly to manufacturers Background (cont’d)

5. 5 Influenza B Strains Recommended for Inclusion in Recent Year’s Vaccines 2000-2001B/Beijing/184/93-like virus (Yamagata ) 2001-2002B/Sichuan/379/99-like virus (Yamagata) 2002-2003B/Hong Kong/330/01-like virus (Victoria) 2003-2004B/Hong Kong/330/01-like virus (Victoria) 2004-2005B/Shanghai/361/2002-like virus (Yamagata) 2005-2006B/Shanghai/361/2002-like virus (Yamagata) 2006-2007B/Malaysia/2506/2004-like virus (Victoria) 2007-2008B/Malaysia/2506/2004-like virus (Victoria) 2008-2009B/Florida/4/2006-like virus (Yamagata) 2009-2010?????

6. Currently Licensed Influenza Vaccines Fluzone (Sanofi Pasteur) Fluvirin (Novartis) Fluarix (GSK) FluLaval (ID Biomedical) Afluria (CSL) FluMist (MedImmune)

7. Manufacturing Capacity of Licensed Influenza Vaccines Has substantially increased over the last 4-5 years –More than 130 million doses of vaccine produced this season (2008/2009) –May increase further with use of novel influenza vaccine platforms such as non-egg based manufacturing processes May enable manufacturers to more easily adjust to manufacturing issues (e.g., poor growth of one strain) related to formulating with additional strains

8. 8 What clinical data are needed to establish safety and immunogenicity of vaccines with an additional B strain? What is the global impact of the U.S. recommending a quadrivalent influenza vaccine containing two B strains? Are there subpopulations, e.g., pediatric and elderly, that would benefit from an influenza vaccine containing two B strains? Issues to Consider

9. 9 What would be the mechanism for recommending a second B strain? –What would be the basis of such recommendation? –What are the implications for vaccine manufacturers and for VRBPAC if WHO does not recommend a second B strain? –What are the implications if the data does not suggest a second B strain in any particular year? Would better coverage of influenza B strains compensate for potential loss or delay in vaccine availability due to adding a second B strain –What are the implications of influenza B growth rates and lack of hgr, production constraints of 4 monovalents, reagent availability, etc.? Issues to Consider (cont’d)

10. 10 Focus of Discussion for the Committee Based on the data presented by the CDC in their model please discuss whether two type B strains should be recommended for the antigenic composition of the seasonal influenza vaccines Please discuss the public health significance and concerns presented by the 2 circulating lineages of influenza B and whether such concerns can be addressed by means of an alternative vaccination strategy

11. 11 BACK-UP SLIDE

12. 12 Alternative Vaccine Formulations for Influenza B Viruses Quadrivalent vaccine: 2 B strains + 2 A strains (4 x 15 mcg/HA = 60 mcg HA/dose) Quadrivalent vaccine: 2 B strains (2 x 7.5 mcg/HA) + 2 A strains (2 x 15 mcg/HA) = 45 mcg HA/dose Monovalent influenza B vaccine (15 mcg HA/dose) administered with seasonal trivalent vaccine