Influenza Vaccine Manufacturing

Industry perspective for 2012-2013 influenza vaccine supply

VRBPAC, 28 February 2012

The FDA CBER requested this annual summary of information from influenza vaccine manufacturers supplying the U.S., for purposes of a general presentation to the VRBPAC. This summary has been prepared

from a variety of public sources, and was reviewed by GSK, Sanofi-Pasteur, Novartis, CSL and MedImmune.

1

2011-2012 Influenza Vaccine Production

• Successful manufacturing campaign• On February 25th, 2011, VRBPAC recommended that vaccines to be used in the

2011-2012 influenza season in the U.S. contain the same virus strains that were used for the 2010-2011 influenza season– Vaccine strains and reagents readily available

• Challenges– Inconsistent potency values for some manufacturers when using reagents

from different sources– Moderate yields of the H3 component

VRBPAC, 28 February 20122

Influenza vaccine strain changes

Season Strain changes H1N1 H3N2 B2011-2012 No strain change2010-2011 2009-2010 2008-2009 Three strain changes2007-2008 2006-2007 2005-2006 2004-2005 2003-2004 No strain change2002-2003 2001-2002

3

Influenza Vaccine Manufacturing Cycle

4

Influenza Vaccine ManufacturingCritical Factors

• Global timing of strain selection – Available time to manufacture influenza vaccine is determined by

• distribution & administration before the peak season • availability of last vaccine strain

– To ensure timely availability of influenza vaccine, manufacturing of one strain starts at risk before final strain composition is confirmed

– Productivity of the least productive monovalent strain determines supply quantity

• Availability of Potency Test Reagents– Complex process to prepare and standardize potency reagents for new strains– Linked to global timing of strain selection for new strains– Availability of calibrated reagents determines start of influenza vaccine

formulation

VRBPAC, 28 February 20125

Examples of Vaccine Strains under Consideration/Evaluation for 2012-2013 NH

Vaccine Manufacture

• H1N1: an A/California/7/2009-like strain– A/California/7/2009 X-179A – A/California/7/2009, NYMC X-181 – A/Christchurch/16/2010, NIB-74– A/Brisbane/10/2010 (LAIV)– A/California/7/2009 (LAIV)

• H3N2: an A/Victoria/361/2011-like strain– A/Victoria/361/2011 IVR-165 – A/Rhode Island/1/2010 (LAIV)

6VRBPAC, 28 February 2012

Examples of Vaccine Strains under Consideration/Evaluation for 2012-2013 NH

Vaccine Manufacture

• B/Yamagata lineage: a B/Wisconsin/1/2010-like strain– B/Wisconsin/1/2010 (TIV, LAIV) – B/Wisconsin/1/2010 BX-41– B/Hubei-Wujiagang/158/2009 – B/Hubei-Wujiagang/158/2009 BX-39– B/Stockholm/12/2011– B/Texas/6/2011

7VRBPAC, 28 February 2012

Influenza Vaccine Manufacturing Cycle

8

Vaccine strains under Consideration/Evaluation for 2012-2013 NH Vaccine Manufacture

• Some manufacturers are developing a quadrivalent Influenza Vaccine that includes a strain of the B/Victoria and B/Yamagata lineage

• In 2011, a new reference strain, B/Wisconsin/1/2010, was identified for the B/Yamagata lineage– New reference strain not included in the vaccine– Vaccine candidate strains were prepared, including reassortant strain

B/Hubei-Wujiagang/158/2009 NYMC BX-39– A reassortant strain of B/Hubei-Wujiagang/158/2009 was also prepared for

LAIV – SRID reagents for B/Hubei-Wujiangang/158/2009 BX-39 were prepared by

CBER in support of clinical development• In 2012, B/Brisbane/60/2008 remains the reference strain for the B/Victoria

lineage

VRBPAC, 28 February 20129

Shared Responsibility of Public and Private Sector is Necessary for Successful Influenza

Vaccine Production and Supply• Timely communication of surveillance data and new candidate viruses• Timely selection of appropriate virus strains, considering antigenic match as well

as growth potential• Early availability of wild-type viruses for reassortant production

– Access of reassortant labs (NYMC, NIBSC, CSL, MedImmune, others) to wild-type strains has been a rate-limiting step

– Opportunity for manufacturers to evaluate growth potential of candidate strains

• Availability of potency test reagents for new strains by May/June• Timely approval of Annual License Supplement• Lot review and release process in-season• Information sharing during telephone conferences, chaired by ERL or WHO,

between WHO CCs, ERLs, reassortant producers and manufacturers has been key in challenging situations (e.g. 3 strain changes in one season)

10VRBPAC, 28 February 2012

Recipient Purpose TotalNew York Medical College

Development of high growth reassortants

Isolation of seasonal influenza viruses in

eggs

For 2011:

estimated US$ 2.05 million

(1,893,934

Swiss Francs)

WHO Essential Regulatory Lab - NIBSC

WHO Influenza CC - Australia

WHO Influenza CC – CDC Atlanta

WHO Influenza CC – NIMR London

Note: CSL also contributes as an independently funded reassortant laboratory

Financial contributions to GISRSmade by IFPMA IVS members

Industry contributes to improving number of quality isolates for development of

candidate vaccine viruses

• Significant financial and technical contributions to improve the number of quality isolates for development of candidate vaccine viruses

• Providing feedback on growth characteristics of candidate strains

• Collaborating on initiatives in key areas such as synthetic seeds, FCC isolates and alternative assays for potency

• Continuing to be engaged in collaborative projects to improve all aspects of Influenza manufacturing