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Licensure of Pandemic Influenza Vaccines:Demonstration of Effectiveness

Vaccines and Related Biological ProductsAdvisory Committee (2/29/2012)

Marion F. Gruber, PhD, Acting DirectorOffice of Vaccines Research and Review/CBER/FDA

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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

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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

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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

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Pre-pandemic and Pandemic periods

U.S. Licensed Seasonal influenza vaccine

A, subtype: H1, H3

Pre-pandemic period Pandemic

strain change supplement

Licensure approach:

Safety

Immunogenicity

Efficacy

A, subtype: H5

A, subtype: H7

A, subtype: H9...

Licensure of “Prototype”pandemic vaccine: adjuvanted

unadjuvanted

Pandemic vaccine update: adjuvanted

unadjuvanted

A, subtype: H5

A, subtype: H7

A, subtype: H9...Licensure approach:

Safety

ImmunogenicityAnnual update:

Strain change supplement

Effectiveness

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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)

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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

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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

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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 H1N1 2009 pandemic for a non-U.S.-licensed adjuvanted monovalent vaccine made by the same manufacturer and process.

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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