Meeting the Challenges of Manufacturing and Delivering Vaccines Globally Emmanuel Hanon, Director, V

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Meeting the Challenges of Manufacturing and
Delivering Vaccines GloballyEmmanuel Hanon,
Director, Viral Vaccines, Research
Development
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(No Transcript)
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Value of Vaccines

• One of the greatest public health achievements
• With the exception of clean drinking water, the
  most effective intervention in reducing and
  preventing the return of infectious diseases1
• Vaccination of a countrys population is
  equivalent to the investment in its education
• Herd immunity leads to global protection 2
• 26 diseases now vaccine preventable2

1European Vaccine Manufacturers paper 2003
2International Federation of Pharmaceutical
Manufacturing Associations. May 2003
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The Target
Developing Countries
Industrialized Countries
900 million
5.0 billion
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The Global Market

• .. is the World, therefore the Challenges are to
  ensure
• RD
• Investment addresses the specific medical needs
  of both the developed and developing world
• There is control of risks as travel for
  individuals becomes easier and more frequent, so
  does travel for infectious diseases
• Manufacturing
• Capacity meets demand
• Marketing
• Immediate use of vaccines in all markets -
  developed and developing countries
• Vaccines are available to those who need them
  while allowing a reasonable margin.

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The Vaccine RD
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Research Development
Identify Antigens
Produce Antigens
Test in Animals
Proof of Concept
Phase I
III
File
Registration/Post marktng
II
Research (Inc. Immunology)
Preclinical Development (Inc. Formulation Science)
Clinical Development (Inc Post Marketing
Surveillance
Transfer Process to Manufacturing
Build Facility
x
x
up to 10-20M
up to 50-100M
up to 500-1B
x
x
x
1-10 yrs
2-3yrs 2-4 yrs ? 1 yr
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Research DevelopmentGSK Biologicals Pipeline
Pre-clinical Respiratory Syncytial
Virus Cytomegalo Virus Men B (paed) Chlamydia
Staph.aureus SARS Cancer Allergy Flu TC
Phase III / Filed Menitorix (HibMenC) DTPw-HepBHi
b-MenAC N.Meningitis combinations Rotarix Streptor
ix Cervarix Priorix tetra Simplirix Boostrix
Polio(DTP IPV) Fendrix
Phase II Hib-MenCY MenACWY Epstein Barr Virus
Mosquirix Hepatitis E Dengue Lung Cancer
(1) Melanoma (1)
Phase I Flu improved HIV S.Pneumoniae
(elderly) TB Varicella Zoster Prostate Cancer
(1) Breast Cancer (1)
Total 9
Total 7
Total 8
Total 9
A well balanced Pipeline from Preclinical to
Phase III
Vaccine containing GSK adjuvant proprietary
systems (1) Therapeutic Vaccines
June 30 2005-GSK Biologicals
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Vaccines Manufacturing
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Manufacturing

• Issues
• Decisions on building manufacturing facilities
  made early in the development process
• can take up to five years to build
• Complexity
• growth of live microorganisms which can vary
• Length of production process
• can be up to one year
• Continuous review by Health Authorities
• need of more biologicals expertise

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Manufacturing

• Way Forward
• Open and constructive relationship with Health
  Authorities
• Mutual recognition of KFDA and EMEA
• Better understanding of manufacturing issues
• Longer range planning of vaccine needs, usage and
  procurement strategies
• Build-up of stock pile and flexibility in
  inventory management
• Set up a network of manufacturing sites in major
  developing countries

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The Vaccine Market
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Traditional Vaccine Market Evolution
Children vaccinated
NEEDS
Private market
EARLYDEMAND
Private market
Public market
MATUREDEMAND
15 - 20 years
Private market
GENERALUSE
Public market
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The Vaccine Market

• How will society pay for 25 vaccines in the next
  10 years to control infectious diseases when the
  uptake of existing vaccines is slow in some
  markets?
• - Possible six or seven new vaccines available
  before 2010 -

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Changing the Paradigm Market Evolution
Children vaccinated
Private market
GENERAL USE
IMMEDIATE
Public market
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Vaccine Availability is a global issue

• Present system of making vaccines available is
  not sustainable
• New vaccines for population segments other than
  infants
• Significant financial pressure
• Number of vaccines available
• Cost of vaccines

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Vaccine Availability

• Availability
• Provide vaccines to developed and developing
  countries
• Ensure all vaccines are available to all
  population segments in all markets
• Manufacturing
• Increase manufacturing capacity in countries
  where a substantial need exists and purchase of
  vaccines is guaranteed
• Marketing
• Create market segmentation - private,
  semi-private, public and externally funded for
  the very poor - that co-exist
• Ensure differential pricing continues in all
  markets, in all segments

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Vaccine Availability Market Segmentation
High
Low
Volume
Price
Low
High
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Vaccine AvailabilityChanging the Paradigm

• For developing world vaccines, partnerships with
  the public sector that both push and pull
  will be necessary
• Establish credible markets in least developed
  countries
• Create Financial Sustainability
• Introduction plans/create demand for new vaccines
• Support of RD activities for new vaccines

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Vaccine Availability

• New vaccines are close to be available
• Will Governments recognize their value?
• Four examples
• Rotavirus
• Human papilloma virus
• Malaria
• Pandemic Flu

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Rotavirus

• Estimated worldwide prevalence of rotavirus
  disease1

Event
Risk of Particular Event
1 293
440,000 deaths
1 65
2 million hospitalizations
1 5
25 million outpatient visits
1 1
111 million domiciliary episodes
1Parashar et al, Emerg Infect Dis 2003 9(5)
565572
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Rotavirus

• Kills 0.5 M children each year
• An effective and safe vaccine registered first in
  developing countries with the European/US
  standards
• GSK vaccine tested in close to 100,000 children
• First registration in July 04, yet will the
  vaccine be used in the countries with high
  medical need?

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Cervical Cancer Worldwide

• 500,000 new cases per year
• 270,000 deaths, 80 in developing countries
• 1,400,000 women with cervical cancer
• Cervical cancer is the 2nd most prevalent cause
  of cancer in women worldwide
• When screening is in place, one pap smear test
  out of 15 is positive and requires medical follow
  up
• 1.6 billion women worldwide is the target
  population

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Est. HPV Cost Structure in the US
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HPV-001 Efficacy Results
Persistent Infection
Incident Infection
CIN lesions
Cytology
Vaccine Efficacy
91
100
93
Lancet, 2004, 364 1757-1765
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The Global Distribution of Falciparum Malaria
Hospitalizations gt20 million Deaths 1-3 million
At risk 2.2 billion people Cases 300-500 million
Loss from economic growth 1980-1995 74 billion
Prevalence gt50
Prevalence 11- 50
Prevalence lt10
Snow RW et al., Nature 434214, 2005 Sachs J et
al., Nature 415680, 2002
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RTS,S Program History
1st Human Protected (SKF/WRAIR)
RTS,S program begins at Rixensart
POC Children 1-4 yrs (Mozambique)
CS cloned, Sequenced (NIH/WRAIR)
RTS,S/AS02A protects 6/7 (WRAIR)
RTS,S/AS02A protects in field (The Gambia)
GSK/MVI Partnership
RTS,S aduvant studies (GSK/WRAIR)
Preclinical program
2
17
1
4
Rec E. coli (SKF/SBBIO) program
Back up strategies (MSP-1, AMA-1, LSA-1, adeno..)
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8
10
3
RTS,S studies in nonimmunes (US/EU)
R16HBs
GSK Collaboration Begins
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12
15
13
18
19
9
5
7
The Gambia
14
16
20
21
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Mozambique
Key Publication
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Critical POC Trial
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Vaccine Efficacy in Mozambique Trial

• N 2022 children aged 1-4 years
• Vaccine efficacy
• Infection 45 (31, 56) plt0.001
• Clinical disease 30 (11, 45) p0.004
• Severe disease 58 (15, 79) p0.019
• Severe (lt24 mos)77 (27, 97) p0.018

Alonso PL et al., Lancet 3641411, 2004
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Pandemic Flu Vaccine
Influenza virus can cause serious infectionthat
leads to death

• Seasonal Influenza Virus
• ?250,000 to 500,000deaths worldwide
• Pandemic Influenza Virus
• Expected 10-30 fold increase in disease and death
• Occurred at least 10 times during last 300 years

Source WHO (www.who.int)
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Pandemic Flu Vaccine
Key numbers

• Worldwide population
• 6900M individuals
• Key numbers in terms of capacity
• 300M trivalent doses
• 450M monovalent 2-doses pandemic vaccine at
  15µgHA
• Key timings for pandemic vaccine
• 4 to 6 month to manufacture first vaccine dose

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Pandemic Flu Vaccine
Failure of current approaches

• NIH clinical trial results H5N1
• Un-adjuvanted split vaccine
• Need for 2-3 injections of 90µg of HA
• Only 75 million individuals could be vaccinated
• gt Need for novel approaches allowingantigen
  sparing

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Pandemic Flu Vaccine
Which strategy to fill the pandemic gap

• Need diversified capacity
• Need antigen-sparing
• Need cross-immunity

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Pandemic Flu Vaccine
GSKs Preparation for Pandemic Antigen-sparing
technology and induction of cross-immunity

• First generation vaccine
• Monovalent Aluminium-adjuvant Whole Virus Vaccine
• Moderate Antigen sparing (H9N2 3.8µg of HA)
• Cross-immunity to be investigated
• Second generation vaccine
• New adjuvant technology increased performance
• Best antigen sparing approach larger capacity
• Induction of cross-immunity

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Conclusions

• RD are the global medical needs being addressed
  ?
• Manufacturing is complex will the industry and
  the authorities create a more positive dialogue
  or will we need a major crisis ?
• Will value of vaccines be recognized in each
  country and represent, like education, an
  investment and not an expenditure ?