Influenza Vaccine Manufacturing Industry Perspective for 2014-15 NH Vaccine Supply The FDA CBER requested this annual summary of information from influenza vaccine manufacturers supplying the U.S., for purposes of a general presentation to the VRBPAC. This summary has been prepared  from a variety of public sources, and was reviewed by AstraZeneca, bioCSL, GSK, Novartis, Protein Sciences, and Sanofi Pasteur.

Industry Comments, VRBPAC 28 February 2014 2013-14 Influenza Vaccines ~134 million doses distributed through 31 January 2014 and in line with 2012-13 season1 Transition to quadrivalent influenza vaccine (QIV) began during 2013-14 season with QIV volume ~20% of total doses QIV volume will likely increase to over 50% for the 2014-15 season As the variety of influenza vaccines has increased in recent years, healthcare providers are choosing different presentations for different patients Timely strain selection by VRBPAC in February 2013 was very helpful Challenges A(H3N2) recommendation was “an H3N2 virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011” (clarified for WHO 2014 SH and 2014-15 NH recommendations) Source: 1 http://www.cdc.gov/flu/professionals/vaccination/vaccinesupply.htm (as of 12 Feb 2014) Industry Comments, VRBPAC 28 February 2014

Vaccination Rates in 2012-13 Higher than in 2011-12 Overall immunization rate of 45% for individuals 6 months of age and older during the 2012-13 season Significant increase in the 6 months - 17 years of age group (to 56.6%) Slight increase in the 18 years of age and older group (to 41.5%) According to the National Immunization Survey, overall immunizations grew slightly in the 2012-2013 season; however, these rates are far below the current Healthy People 2020 goals of 80-90% coverage, depending on age group. Source: http://www.cdc.gov/flu/fluvaxview/coverage-1213estimates.htm (as of 12 Feb 2014) Industry Comments, VRBPAC 28 February 2014

Total Cumulative Influenza Vaccine Claims in 2013-14 Higher than in 2012-13 ~6% Data suggest 2013-14 immunizations are up ~6% vs. prior year Source: IMS Health Custom Study, Medical Claims Data, Week Ending 25 Jan 2014 Industry Comments, VRBPAC 28 February 2014

Influenza Vaccine Strain Changes Season A(H1N1) A(H3N2) B-Vic B-Yam Comment 2013-14 µ First selection for QIV 2012-13 n/a 2011-12 No strain change 2010-11 2009-10 2008-09 Three strain changes 2007-08 2006-07 2005-06 2004-05 2003-04 2002-03 2001-02 Industry Comments, VRBPAC 28 February 2014

Influenza Vaccine Manufacturing Timeline Jan Dec Nov Feb Mar Apr May Jun Jul Aug Sep Oct 4 FDA Strain Selection Annual License Approval Vaccination Produce & Standardize Reagents Surveillance & Reassortants Production (may be at risk) 4 Production (at risk) Strain Balancing 4 Formulation Produce Working Seed Filling & Packaging Distribution Industry Comments, VRBPAC 28 February 2014

Influenza Vaccine Manufacturing Critical Factors Global timing of strain selection ensures large vaccine supply Available time to manufacture influenza vaccine is determined by Need to distribute & administer vaccine well before the peak season Availability of last vaccine strain To ensure timely availability of influenza vaccine, manufacturing of at least one strain starts at risk before VRBPAC recommendations Productivity of the least productive monovalent strain determines supply quantity Availability of potency test reagents Complex process to prepare and standardize potency reagents for new strains Linked to global timing of strain selection for new strains Availability of calibrated reagents determines start of influenza vaccine formulation Industry Comments, VRBPAC 28 February 2014

Vaccine Strains under Evaluation for 2014-15 NH Vaccine A(H1N1): A/California/7/2009-like A/California/7/2009 and reassortants (IIV and LAIV) A/Christchurch/16/2010 and reassortants (IIV) A/Brisbane/10/2010 and reassortants A(H3N2): A/Victoria/361/2011 cell-derived-like A/Texas/50/2012 and reassortants (IIV and LAIV) A/New York/39/2012 and reassortants A/Almaty/2958/2013 and reassortants Industry Comments, VRBPAC 28 February 2014

Vaccine Strains under Evaluation for 2014-15 NH Vaccine B Yamagata lineage B/Massachusetts/2/2012 and reassortants (IIV and LAIV) B Victoria lineage B/Brisbane/60/2008 and reassortants (IIV and LAIV) B/Hong Kong/259/2010 and reassortants (IIV) B/Nevada/3/2011 and reassortants (IIV and LAIV) B/Texas/2/2013 and reassortants Industry Comments, VRBPAC 28 February 2014

Industry Comments, VRBPAC 28 February 2014 Industry Agency Shared Responsibility for Successful Influenza Vaccine Production & Supply Communication Continued timely sharing of surveillance and candidate virus information Bi-weekly WHO teleconferences key in challenging situations Strain selection Timely review and selection of the appropriate viral strains Balanced consideration of strain surveillance, selection timing, and impact to vaccine availability Virus and reagent availability Early access of all reassortant labs (NYMC, NIBSC, bioCSL, AstraZeneca, etc) to wild-type viruses Opportunity for manufacturers to evaluate growth characteristics of potential strain candidates Availability of potency test reagents for new strains by June Vaccine approval and release Timely approval of annual license supplement In-season lot review and release process Industry Comments, VRBPAC 28 February 2014