Office of the Assistant Secretary for Planning and Evaluation (ASPE) Influenza Vaccine Project: Understanding the Dynamics of Influenza Vaccine Supply and Demand

1615 M Street, NW, Suite 740 · Washington, DC 20036

Phone: 410.467.2907 · layton@rti.org · www.rti.org

RTI International is a trade name of Research Triangle Institute.

Presented toNational Vaccine Advisory Committee Washington, DC February 8, 2006

Presented by Christine M. Layton, PhD, MPH

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Purpose of Project

To provide policy makers and other decision makers information about influenza vaccine issues that: Summarizes current issues Is in a useful format

Not to address pandemic or avian influenza concerns.

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Summary of Project: Understanding the Dynamics of Influenza Vaccine Supply and Demand

Annotated bibliography

Key informant interviews

Issue brief subject areas Influenza vaccine overview Influenza vaccine purchasing and

distribution Influenza vaccine manufacturing Influenza vaccine economics Influenza vaccine demand

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Annotated Bibliography

Collecting various sources of information Peer-reviewed journals Expert reports, e.g., IOM “Fugitive” literature Web sites Conference abstracts Print media, i.e., newspapers

5

Key Informant Interviews

30 interviews with representatives of Vaccine manufacturers Vaccine distributors Community immunizers Federal public health officials State public health officials Others (i.e., academicians)

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Issue Brief: Overview

Summarize influenza vaccine supply issues

Summarize other issue briefs

Provide case studies for previous influenza seasons 1999-2005

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Influenza Vaccine is Unique

InfluenzaVaccine

Vaccines

Biologics

Pharmaceuticals

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Summary of 1999-2005 Influenza Seasons

Event

Influenza Season

1999–2000 2000–2001 2001–2002 2002–2003 2003–2004 2004–2005

Prevailing influenza strain

A(H3N2) A(H1N1) A(H3N2) A(H1) A(H3N2) A(H3N2)

Production problems No Yes No No No Yes

Delays in delivery No Yes Yes No No Yes

Spot shortages No Yes Yes No Yes Yes

Vaccine rationing No No No No No Yes

ACIP broadens identified target groups

No Yes No No No Yes

ACIP updated recommendations

No No Yes Yes Yes Yes

Sources: CDC, 1999b; CDC, 2000b; CDC, 2001a; CDC, 2001c; CDC, 2002a; CDC, 2002b; CDC, 2002c; CDC, 2003a; CDC, 2003b; CDC, 2004a; CDC, 2004c; CDC, 2004d; CDC, 2004f; CDC, 2005b; FDA, 2001.

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Influenza Vaccine Purchasers

Purchasers Wholesalers Immunization Providers

Private healthcare providers Community immunizers State and federal governments

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U.S.-Licensed Influenza Vaccines for 2005–2006

a In 2004, Sanofi merged with Aventis Pasteur to create the Sanofi Aventis Group. The vaccine division of the Sanofi Aventis Group changed its name to Sanofi Pasteur.

b FluMist is approved for use among those 5 to 49 years of age who are otherwise healthy and not pregnant. Source: CDC, 2005c.

Approved Age of Recipient  

Vaccine Type

Product (Manufacturer)

6 months–3 years 4 years 5–17 years

18–49 years

50+ years

No. of Projected

Doses

Inactivated Fluarix (GSK) X X 8M  

Fluvirin (Chiron) X X X X 18-26M  

FluZone (Sanofi Pasteur)a X X X X X 60M  

LAIV FluMist (MedImmune)b X X 3M  

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Influenza Vaccine Distribution

Distributors Manufacturers (direct) Wholesalers (indirect)

Distribution dependent on manufacturers’ choice

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US Influenza Vaccine Distribution Pathways

DoD = U.S. Department of Defense; ERs = emergency rooms; LHDs = local health departments; MMCAP = Minnesota Multi-State Contracting Alliance for Pharmacy; VA = U.S. Department of Veterans Affairs; VNAs = Visiting Nurse Associations

LHDsProviders VNAs Physicians Clinics Mass Immunizers Hospitals/ERs

Purchasers Chain Pharmacies

Hospital Pharmacies

MilitaryDoD/VA

IndependentPharmacies

Large Purchaserse.g., MMCAP

WholesalersWholesaler

1Wholesaler

2Wholesaler

3Wholesaler

4

ManufacturersManufacturer

AManufacturer

BManufacturer

C

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Influenza Vaccine Purchase and Distribution Solutions

Improvements in: vaccine supply uniformity of distribution and vaccine

tracking infrastructure support for public health in general

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Influenza Vaccine: Manufacturing

Brief Biology of Influenza and History of Influenza Vaccination

Influenza Vaccine Manufacturing 101

Manufacturer Decision Making

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Influenza Vaccine Manufacturing Process

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Major U.S. Vaccine Manufacturers in 1980 and 2002

Major U.S. VaccineManufacturers in 1980

Major U.S. VaccineManufacturers in 2002

Merck, Sharp, & Dohme Pasteur Vaccines Merieux Institute Connaught Armomd Frappe SmithKline SSW Human Vaccine Institute Wyeth-Ayerst

American Cyanamid Praxis Parke-David Chiron Behring Biocine Novartis Wellcome

Merck & Co., Inc. Sanofi Pasteura

GlaxoSmithKline (GSK) Wyeth-Ayerst Chiron

a In 2004, Sanofi merged with Aventis Pasteur to create the Sanofi Aventis Group. The vaccine division of the Sanofi Aventis Group changed its name to Sanofi Pasteur.

Source: Shaw, 2004

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Influenza Vaccines, Manufacturers, and Seasons during which each Vaccine Was Sold

Influenza Seasona,b

Vaccine Trade Name Manufacturer

1993–94

1994–95

1995–96

1996–97

1997–98

1998–99

1999–00

2000–01

2001–02

2002–03

2003–04

2004–05

2005–06

Fluarix GlaxoSmithKline (GSK) •

FluMistc MedImmune Vaccines, Inc.

• ••

Fluogen Parkedale Pharmaceuticals Inc.d •

Parke-Davis • • • •

FluShielde Wyeth Laboratories, Inc. • • • • • • • • • • •

Fluvirinf Chiron Corporation g •

Evans Vaccines Ltd. •

PowderJect Pharmaceuticals plc

• •

Medeva Pharma Ltd. • • • • • • •

Fluzone Sanofi Pasteur Inc.h • • • • • •

Connaught Laboratories

• • • • • • •

Flu-Imune Lederle Laboratories •

a Vaccine Adverse Event Reporting System (VAERS) data used in this table include manufacturer and trade name information taken only from specific incidence reports of vaccine adverse reactions. Data that did not specify specific influenza seasons were not used.b Influenza seasons 1993–1994 through 2000–2001 (CDC, 1993, 1994, 1995, 1996, 1997, 1998, 1999, 2000). Influenza seasons 2001–2002 through 2004–2005 (FDA, 2005b).c Wyeth and MedImmune had a collaboration for the commercialization of FluMist for the 2003–2004 influenza season. The companies announced the dissolution of their collaboration in April 2004.d Parkedale Phamaceuticals, Inc., was ordered to discontinue production of influenza vaccine following a 2000 FDA inspection.e 1993–1994 trade name not available. Wyeth left the market after losing $50 million over the prior three influenza seasons; 2001–2002 was the worst season, during which the company lost $30 million and had 7 million doses of the vaccine that never sold (Ferguson, 2004). f In 2003, Chiron acquired PowderJect as a wholly owned subsidiary. In 2001, PowderJect acquired Medeva—which had previously acquired Evans Medical Ltd.—and restored the Evans name to Evans Vaccines Ltd., a wholly owned subsidiary of PowderJect. Prior to this, Evans Medical Ltd. had acquired the vaccine business of Wellcome. For more information on company acquisitions and mergers, see Vaccine Identification Standards Initiative: Manufacturer Abbreviations (CDC, 2003).g On October 5, 2004, Chiron’s influenza vaccine plant was forced to cease production by government regulators due to contamination issues.h In 1999, Aventis Pasteur, Inc., obtained FluZone vaccine ownership from Connaught Laboratories, Inc. In 2004, Sanofi merged with Aventis Pasteur to create the Sanofi Aventis Group. The vaccine division of the Sanofi Aventis Group changed its name to Sanofi Pasteur.

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Influenza Vaccine Production

Influenza Vaccine Product Name (Manufacturer)

Nation in Which Manufacturer is Based

Nation in Which Product is Produced

Number of Doses Produced (as estimated

for 2005–2006)

Fluarix (GSK) United Kingdom Germany 8M

Fluvirin (Chiron) United States United Kingdom 18 to 26M

FluZone (Sanofi Pasteur) France United States 60M

FluMista (MedImmune) United StatesUnited States & United

Kingdom3M

aLAIV

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Influenza Vaccine Economics

The Influenza Vaccine Industry Barriers to Entry Vaccine Profits Demand for Influenza Vaccine

Vaccine Supplier Decisions Profit-Maximizing Decision Making Uncertain Demand

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Influenza Vaccine Economics: The Influenza Vaccine Industry

Barriers to Entry “Sunk” costs (regulatory and licensing

requirements) FDA licensing fees ~$1M Clinical trials ~$90M Production facilities ~$100M

Vaccine Profits Vaccine prices Market size Production costs Investments in new technologies

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Influenza Vaccine Economics: Vaccine Supplier Decisions

Profit-Maximizing Decision Making

Uncertain Demand Pricing Decisions Vaccine Distribution

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Demand and Supply

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Influenza Vaccine: Demand

Factors that Affect Demand: Price of vaccination Convenience Knowledge of influenza’s impact Severity and timing of influenza season Demographics Severity of previous year’s influenza

season Perception of need Provider’s recommendation

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Influenza Vaccine Doses Produced and Distributed for the U.S. Market 1999-2004

77.2 77.987.7

9586.9

61.0

76.8 70.4 77.7 83 83.1

57.1

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

1999 2000 2001 2002 2003 2004

Doses Produced Doses Distributed

Total Targeteda Population (183.3 Million)

All Persons Aged 6 Months and Older (288.8 Million)

Mil

lio

ns

77.2 77.987.7

9586.9

61.0

76.8 70.4 77.7 83 83.1

57.1

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

1999 2000 2001 2002 2003 2004

Doses Produced Doses Distributed

Total Targeteda Population (183.3 Million)

All Persons Aged 6 Months and Older (288.8 Million) M

illi

on

s

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Influenza Vaccine: Demand

Stakeholders Government (federal, state and local) Academia Health care providers Community immunizers Advocacy organizations Health insurance companies Vaccine industry (manufacturers, distributors) Wholesalers Professional societies Consumers

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Changes in ACIP Influenza Vaccination Target Groups: 1999–2000 through 2005–2006 Influenza Seasons

Target Group1999–2000

2000–2001 2001–2002 2002–2003 2003–2004 2004–2005

2005–2006

65 years of age X X X X X X X

Chronically ill X X X X X X X

Pregnanta X X X X X X

50 years of age X X X X X X

Household contacts of high-priority persons

X X X X X X X

Health care workers X X X X X X

6 to 23 months of age X X

a Those who will be in the second or third trimester of pregnancy during influenza season. As of 2004, annual vaccination was recommended for all pregnant women, if they were pregnant during influenza season.

Sources: ACIP, 1999; ACIP, 2000; ACIP, 2001; Bridges, Fukuda, Uyeki, Cox, & Singleton, 2002; Bridges et al., 2003; CDC, 2005b; CDC, 2005c; Harper, Fukuda, Uyeki, Cox, & Bridges, 2004; Harper, Fukuda, Uyeki, Cox, & Bridges, 2005.

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Site of Influenza Vaccination of Persons 65 Years of Age and Older

Source: Compiled from Behavioral Risk Factor Surveillance System survey data (Centers for Disease Control and Prevention [CDC], 1999, 2002, 2003).

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1999 2002 2003Year

Traditional medical setting Nonmedical setting Health Department Other

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Influenza Vaccine: Demand

Roles for Stakeholders Federal Government

“The government sets the tone for private payers as well. Reimbursement done by Medicare, Medicaid, etc. kind of sets the tone for private payers, so adequate reimbursement to the physicians so that they don’t feel that it’s some sort of loss leader for them would be very encouraging.” (Former State Health Official and current academic)

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Influenza Vaccine: Demand

Roles for Stakeholders (con’t) State and Local Governments

Public clinics Public information campaigns

Vaccine Manufacturers Information/education of health care

providers– Role of distributors and sales representatives?

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Influenza Vaccine: Demand

Roles for Stakeholders (con’t)

Wholesalers Promote immunization by customers

(healthcare providers)

Professional organizations Promote immunization by and among

members

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Influenza Vaccine: Demand

“When’s the last time you saw an immunization message on Superbowl Sunday. If we had a public campaign we could forget ACIP recommendations. We create demand for $200 tennis shoes, why not a vaccine that could save your life? It’s nuts!” (Former state health official)

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Strategies to Stabilize Influenza Vaccine Supply

Harmonize International Standards

Shorten FDA Approval Process for New Vaccines

Implement Purchase or Buy-Back Guarantees

Increase Demand

Create “Strategic Reserve”

Develop New Technologies

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Unanswered Questions

Distribution challenges

Effect of legislation relating to: Thimerosol Vaccine distribution

Science-based interventions and program evaluation based on pre-defined measures

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The Role of Public Health

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Acknowledgements

Amy Nevel, MPH—ASPE Project officer

Key Informants

RTI Staff Amanda Honeycutt, PhD—Economic

analyst Lucia Rojas Smith, DrPH, MPH—

Research analyst Nathan West, MPH—Project associate Nancy Lenfestey, MHA—Project analyst Tara Robinson, BA—Project assistant