18Feb2009VRBPAC Influenza Vaccine Manufacturing Industry Perspective for Vaccine Supply

18Feb2009VRBPAC Inactivated Influenza Vaccine Potentially significant supply shortage averted even with 3 strain change due to Strain Change decision included all changes and did not defer until later in the manufacturing season Growth Characteristics of selected seeds were unexpectedly strong requiring minimal advancement by manufactures All new vaccine potency reagents were required to be supplied through non-traditional sources and means with undemonstrated performance Industry / Agency shared responsibility to facilitate supply

18Feb2009VRBPAC Influenza Vaccine Manufacturing – Critical Factors Global timing of strain selection –Distribution and administration of vaccine prior to peak season coupled with lengthy manufacturing process condenses available production time forcing Industry to manufacture at risk –Working seeds require a minimum of 4 weeks from receipt of viable candidate through development and release prior to use in large-scale manufacturing –Growth Potential becomes critical as the supply quantity of Vaccine is driven by the least productive Monovalent strain candidate Availability of Potency Test Reagents –Lengthy process for manufacture and standardization for any new strains, thus clearly tied to global strain selection timing

18Feb2009VRBPAC Influenza Vaccine Manufacturing Model Timeline Jan DecNov FebMarAprMayJunJulAugSepOct Manufacture Strain 3 Manufacture Strain 2 Potentially at Risk Manufacture Strain 1 AT RISK Strain #1 Balancing Strain #2 Balancing Strain #3 Balancing Surveillance data & Produce Reassortants Produce Working Seed Annual License Approval Produce / Standardize Reagents Formulate, Fill Package Trivalent Bulk Vaccine Distribute Vaccine

18Feb2009VRBPAC NH Current Manufacturing Status Production initiated by most manufacturers at risk of strain(s) not being selected to ensure timely supply –H1N1: A/Brisbane/59/2007-like A/Brisbane/59/2007 IVR-148 (2008 TIV Carryover) A/South Dakota/6/2007 reassortant (2008 LAIV Carryover) A/Guam/1/2007 (clade 2C) reassortants available for TIV and LAIV Several additional H1N1 Brisbane-like LAIV reassortants underway –H3N2: A/Brisbane/10/2007 – like A/Uruguay/716/2007 – used in some TIV and LAIV vaccine in 2008 Other H3N2 candidates: –A/Brisbane/24/2008 IVR-151 – Just received and under evaluation –A/Brisbane/24/2008 LAIV reassortant in progress –Several additional H3N2 LAIV reassortants underway –B Strain: To date no manufacturer has started production on B Strain for the 2009 – 2010 campaign year

18Feb2009VRBPAC B/ Strain Candidates for TIV & LAIV Potential Victoria lineage candidates still under evaluation High Growth reassortants needed from potential candidates

18Feb2009VRBPAC Industry / Agency Shared Responsibility is necessary for successful Influenza Vaccine production & supply Continued timely communication of surveillance and reassortment information Timely committee selection of the appropriate viral strains –Duel consideration of antigenic match as well as growth potential Quicker availability of wild-type viruses and reassortants –Availability of wild-type viruses to reassortant labs (MedImmune, CSL, NYMC, NIBSC, etc) is rate-limiting step –Opportunity for manufacturers to evaluate growth characteristics of potential strain candidates –Availability of potency test reagents for new TIV strains by June. Timely approval of Annual License Supplement In-Season Lot review and release process –Estimation of workload volume