Influenza Vaccine Manufacturing

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

2. 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 VRBPAC 25 February 2011

3. Significant Immunization Growth in 2010-11 to 19% Overall • 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 Sources: Surveillance Data Inc., CDC Distribution and Vaccination Data, and internal supply estimates VRBPAC 25 February 2011

4. Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Strain Selection FDA Annual License Approval Surveillance & Reassortants Vaccination WHO Production (at risk) Strain Balancing Production (may be at risk) Formulation Production Filling & Packaging Distribution Influenza Vaccine Manufacturing Timeline Produce & Standardize Reagents Production Produce Working Seed VRBPAC 25 February 2011

5. Influenza Vaccine ManufacturingCritical 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 VRBPAC 25 February 2011

6. 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 VRBPAC 25 February 2011

7. 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 VRBPAC 25 February 2011

8. 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 VRBPAC 25 February 2011