Norman W. Baylor, Ph.D. Director, Office of Vaccines Research and Review FDA/CBER 23 July 2009

1. VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEEFDA Regulatory Pathway To Facilitate the Licensure and Availability of Pandemic (H1N1) 2009 Influenza Virus Vaccines Norman W. Baylor, Ph.D. Director, Office of Vaccines Research and Review FDA/CBER 23 July 2009

2. Introduction • FDA is convening the Vaccines and Related Biological Products Advisory Committee (VRBPAC) to present our approach to facilitate the licensure and availability of vaccines against the pandemic (H1N1) 2009 Influenza virus. • FDA is collaborating with other government agencies (NIH, CDC, BARDA, NVPO, and DHHS), the World Health Organization, other National Regulatory Authorities, and the vaccine industry to facilitate the licensure of safe and effective vaccines against pandemic (H1N1) 2009 influenza virus.

3. Regulatory Pathway to Licensure • Over the coming weeks, the US Government and the vaccine manufacturers will need to make critical decisions: • formulation of a pandemic (H1N1) 2009 influenza vaccine, and • recommendations for vaccination of targeted groups and potentially the entire U.S. population • Due to the rapid spread and the uncertainty of the pandemic this fall, FDA has considered regulatory pathways to facilitate licensure and has determined that monovalent unadjuvanted vaccines against pandemic (H1N1) 2009 influenza virus can be licensed as strain change supplements to existing BLAs: • is consistent with licensure of new seasonal vaccines • is consistent with past regulatory actions • facilitates availability if vaccination is recommended

4. Outline of Agenda • FDA will present considerations for manufacturing and testing of vaccines, the regulatory approach to the clinical evaluation of vaccines, and an overview of post marketing safety monitoring and evaluation. • CDC will provide an update on surveillance and epidemiology of pandemic (H1N1) 2009 influenza virus. • NIH will provide an overview of their proposed clinical studies. • BARDA will present an overview of DHHS role in preparedness and procurement of pandemic (H1N1) 2009 influenza virus vaccines. • Influenza vaccine manufacturers will provide brief overviews of their plans for manufacturing and clinical evaluation of pandemic (H1N1) 2009 influenza virus vaccines.

5. 2009 H1N1 Influenza Pandemic Declaration “On the basis of available evidence, and these expert assessments of the evidence, the scientific criteria for an influenza pandemic have been met. I have therefore decided to raise the level of influenza pandemic alert from phase 5 to phase 6. The world is now at the start of the 2009 influenza pandemic.” -Dr. Margaret Chan, Director General, WHO, 11 June 2009

6. 2009 H1N1 Influenza Pandemic “..The 2009 influenza pandemic has spread internationally with unprecedented speed. In past pandemics, influenza viruses have needed more than six months to spread as widely as the new H1N1 virus has spread in less than six weeks…” - WHO, July 16, 2009

7. US Cases: 40,617 US Deaths: 263 July 16, 2009 Global Total Cases: 139,629 Global Deaths: 867 Cumulative Number of Confirmed Human Cases of Pandemic 2009 Influenza (H1N1) Reported to WHO

8. Southern Hemisphere The Southern hemisphere, currently reporting pandemic (H1N1) 2009 influenza virus activity, may be a predictor of activity in the Northern hemisphere in the fall…

9. Planning considerations: • Current situation and expectations: • Continued circulation of pandemic (H1N1) 2009 influenza virus • The number of cases will continue to increase • Vaccines will be an important intervention against pandemic (H1N1) 2009 influenza virus • An adequate supply of vaccine is necessary for preparedness • Uncertainties: • Possibility of development of increased virulence and associated morbidity, especially in children and young adults • Possibility of widespread antiviral drug resistance • Severity of the 2009 H1N1 influenza pandemic • Antigenic drift

10. Conclusion • The pandemic (H1N1) 2009 influenza virus is continuing to spread globally, and there are uncertainties about how the virus will behave during the U.S. 2009-10 influenza season. • FDA is committed to ensuring the availability of safe and effective vaccines against the pandemic (H1N1) 2009 influenza virus in the event of recommendations to use the vaccines. • As part of the government’s efforts in pandemic preparedness FDA, along with other Agencies within DHHS, believe that licensure of monovalent, non-adjuvanted vaccines against the pandemic (H1N1) 2009 influenza virus as a strain change is the most expeditious pathway for providing safe and effective vaccines to the public. • Availability of adjuvanted vaccines, if needed, under a Emergency Use Authorization is an option. • Discussions concerning recommendation for use and implementation of immunization programs for pandemic (H1N1) 2009 influenza vaccine are ongoing within other parts of the government and by other advisory committees, and are separate from licensure of the vaccine.

11. Discussion Items • Please discuss whether FDA’s approach to license non-adjuvanted pandemic (H1N1) 2009 influenza vaccines via a strain change supplement without new clinical data is appropriate with clinical data to be submitted post licensure. • The pandemic H1N1 2009 vaccine would be manufactured by U.S. licensed manufacturers using their currently licensed seasonal influenza vaccine process, and the current dose (15 μg HA/ 0.5ml dose for inactivated, and 106.5-7.5 FFU per 0.2mL dose for LAIV) • Please discuss whether recipients of the pandemic (H1N1) 2009 influenza vaccine should be administered two doses of vaccine at the initiation of the program.

12. Discussion Items (cont’d) • Please discuss considerations for immunizing special populations such as children below the age of 6 months, and pregnant women. • Please discuss considerations for use of adjuvanted vaccines. • Please discuss the proposed post-licensure evaluations for safety. Please identify any gaps that may not have been included in our proposal. • Please comment on approaches to assessing vaccine effectiveness. Consider the potential need for diagnostic methods to distinguish pandemic 2009 H1N1 strains from circulating seasonal strains and other influenza-like illnesses.