1. VRBPAC 25 February 2011 Influenza Vaccine Manufacturing Industry Perspective for 2011-2012 Vaccine Supply

2. VRBPAC 25 February 2011 2010-2011 Influenza Vaccines Highly successful manufacturing campaign  More doses distributed than ever before  Mid-season indications of significantly increased uptake Timely strain selection by VRBPAC  Strong production numbers despite moderate yields Challenges  Completion of pandemic influenza vaccine production  Delayed release for some manufacturers due to late information regarding tip caps  Inconsistent SRID potency values for some manufacturers when using reagents from different sources

3. VRBPAC 25 February 2011 Significant Immunization Growth in 2010-11 to 19% Overall Sources: Surveillance Data Inc., CDC Distribution and Vaccination Data, and internal supply estimates Pediatric immunization had ~18% growth Adult immunization had ~24% growth 65+ immunization had ~14% growth after 20% decrease in 2009 as a result of H1N1 prioritization With supply now far exceeding demand, opportunity for immunization growth is greatly improved

4. VRBPAC 25 February 2011 Influenza Vaccine Manufacturing Timeline JanDecNovFebMarAprMayJunJulAugSepOct Surveillance & Reassortants Vaccination Distribution Produce & Standardize Reagents Production (at risk) Production (may be at risk) Production Strain Balancing Filling & Packaging Formulation Produce Working Seed Production Annual License Approval Strain Selection FDA WHO

5. VRBPAC 25 February 2011 Influenza Vaccine Manufacturing Critical Factors Objective: Distribution & Administration of influenza vaccines prior to peak season Global timing of strain selection  Ensures timely availability of very large quantities of vaccines while manufacturers accept some risk by starting production early  Requires consideration of strain surveillance, selection timing, and impact to vaccine availability  Allows final development of working seeds that require a minimum of 4 weeks from receipt of a viable candidate virus through release prior to use in large-scale manufacturing  Minimizes impact of constraints imposed by the least productive monovalent strain candidate Availability of Potency Test Reagents  Lengthy process of preparation and standardization  Linked to global timing of strain selection for new strains  Constrains start of formulation of finished vaccine

6. VRBPAC 25 February 2011 2011-12 NH Current Manufacturing Status Production initiated by most manufacturers “at risk” to ensure timely supply H1N1: A/California/7/2009–like  A/California/7/2009 X-179A  A/California/7/2009 X-181  A/Christ Church/16/2010 NIB-74 H3N2: A/Perth/16/2009–like  A/Victoria/210/09 X-187

7. VRBPAC 25 February 2011 B-Strain Candidates for TIV & LAIV B Victoria-lineage candidates  B/Brisbane/60/2008 (CBER reagents)  B/Brisbane/60/2008 BX-35 (NIBSC reagents) B Yamagata-lineage candidates  B/Hubei-Wujiagang/158/2009 BX-39 (no reagents available) Some manufacturers are developing a quadrivalent influenza vaccine that includes a second B-Strain

8. VRBPAC 25 February 2011 Industry  Agency Shared Responsibility is necessary for Successful Influenza Vaccine Production & Supply Communication  Continued timely sharing of surveillance and candidate virus information Strain selection  Timely review and selection of the appropriate viral strains  Balanced consideration of strain surveillance, selection timing, and impact to vaccine availability Virus availability: rapid availability of wild-type viruses and reassortants  Access to wild-type viruses to reassortant labs (NYMC, NIBSC, CSL, MedImmune, etc) is rate-limiting step  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