1. Licensure of Pandemic Influenza Vaccines: Demonstration of Effectiveness
Vaccines and Related Biological Products
Advisory Committee (2/29/2012)
Marion F. Gruber, PhD, Acting Director
Office of Vaccines Research and Review/CBER/FDA

2. Purpose of Today’s VRBPAC Discussion
Review pathways to licensure of the influenza A (H1N1) 2009 vaccines and an influenza A (H5N1) vaccine
Discuss approaches to the pre-licensure evaluation of effectiveness of adjuvanted pandemic influenza A virus subtype vaccines manufactured using the same process as the manufacturer’s U.S-licensed unadjuvanted seasonal influenza vaccine
Discuss approaches to the pre-licensure evaluation of effectiveness of pandemic influenza A subtype vaccines manufactured using a process that is not U.S.-licensed

3. US licensed Seasonal & Pandemic Influenza Vaccines
Seasonal Influenza Vaccines (Inactivated, intramuscular)
Afluria (CSL)
Agriflu (Novartis)
Fluarix (GSK)
FluLaval (IDB-GSK)
Fluvirin (Novartis)
Fluzone (Sanofi Pasteur)
Seasonal Influenza Vaccine (Live attenuated, intranasal)
FluMist (MedImmune)
Monovalent pandemic Influenza vaccines
H5N1 Influenza Virus Vaccine, (inactivated, i.m)
Sanofi Pasteur)
H1N1: Influenza A (H1N1) 2009 Monovalent Vaccines (inactivated, i.m)
CSL
IDB-GSK
Novartis
Sanofi Pasteur
H1N1: Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal (live attenuated, i.n)
MedImmune

4. Pandemic Preparedness: Regulatory Considerations
Development and timely availability of a vaccine matched to the pandemic influenza strain is a cornerstone of pandemic influenza prevention
National regulatory authorities must be prepared to respond with regulatory pathways to expedite the availability of pandemic influenza vaccines
In the event of a pandemic, prior licensure of “prototype” influenza vaccines will shorten the time to licensure of a vaccine against the pandemic strain

5. Pre-pandemic and Pandemic periods
Pre-pandemic period
Pandemic
Pre-pandemic and Pandemic periods
U.S. Licensed
Seasonal influenza
vaccine
A, subtype: H1, H3
Licensure of “Prototype”
pandemic vaccine:
adjuvanted
unadjuvanted
Pandemic vaccine
update:
adjuvanted
unadjuvanted
strain change
supplement
A, subtype: H5
A, subtype: H7
A, subtype: H5
A, subtype: H7
A, subtype: H9...
Licensure approach:
Safety
Immunogenicity
Efficacy
A, subtype: H9...
Licensure approach:
Safety
Immunogenicity
Annual update:
Strain change
supplement
Effectiveness

6. Pandemic Preparedness: Regulatory Considerations (cont.)
Influenza A (H1N1) 2009 vaccines and an influenza A (H5N1) vaccine
Manufacturers utilized same egg based manufacturing process as their seasonal vaccines
Clinical endpoint efficacy data accrued with a U.S.-licensed seasonal influenza vaccine has been used to infer effectiveness  
Approach discussed at previous VRBPAC meetings (e.g., February 2007 and July 2009)
Pandemic influenza vaccines in clinical development
Made by the same process as licensed seasonal vaccine except that the vaccine contains adjuvant
Made by a process not US licensed (adjuvanted/nonadjuvanted)

7. Pandemic Preparedness: Regulatory Considerations (cont.)
FDA is working with vaccine manufacturers interested in developing pandemic influenza vaccines to establish pathways to support effectiveness prior to licensure
FDA will outline approaches to licensure that are specifically tailored to pandemic influenza vaccines for which it is not feasible for manufacturers to conduct clinical endpoint efficacy studies
Scenarios outlined pertain to adjuvanted and unadjuvanted pandemic influenza vaccines for use in the event of a pandemic

8. Overview of Today’s Agenda
BARDA perspective regarding pandemic influenza vaccine preparedness
Dr. Robin Robinson, PhD
FDA proposed approach to licensure of pandemic influenza vaccines
Dr. Theresa Finn, PhD
Manufacturer’s presentations on pandemic influenza vaccine development
GSK, Kati Abraham
Novartis, Penny Heaton, MD
Committee discussion

9. Discussion items
1. To infer effectiveness of an adjuvanted pandemic influenza A subtype vaccine, please discuss the use of:
a) clinical endpoint efficacy data accrued with a U.S.-licensed unadjuvanted seasonal vaccine made by the same manufacturer and process, and
b) observational effectiveness data accrued during the H1N pandemic for a non-U.S.-licensed adjuvanted monovalent vaccine made by the same manufacturer and process.

10. Discussion items
2. Please discuss approaches to infer effectiveness for pandemic influenza vaccines that are manufactured using a process not licensed in the U.S.:
a) pandemic influenza vaccines dependent on an HA antibody response
b) pandemic influenza vaccines with protective mechanisms that are not dependent on an HA antibody response