New Vaccine Supply and Financing: A Case Study of Combination Vaccines in Developing Countries

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New Vaccine Supply and Financing A Case Study
of Combination Vaccines in Developing Countries

• Viral Hepatitis Prevention Board Meeting
• Malta
• October 22-23, 2001

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Global status of countries using HepB vaccine in
their national immunization system, 2001
The boundaries and names shown and the
designations used on this map do not imply the
expression of any opinion whatsoever on the part
of the World Health Organization concerning the
legal status of any country, territory, city or
area or of its authorities, or concerning the
delimitation of its frontiers or boundaries.
Dotted lines on maps represent approximate border
lines for which there may not yet be full
agreement.
Routine HepB implementation status
Yes
No
August 2001
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HepB Combination vaccines A sample of current
developing country users

• WPRO - Started with monovalent, especially with
  birth dose, now some adopters with quadrivalent
  (DTP-hepB)
• PAHO - Originally not very interested, now
  adopting combos (quad or pentavalent)
• AFRO - Two original countries started with
  monovalent. One now shifting with GAVI, as is
  most of AFRO, to quadrivalent (DTP-HepB) or
  pentavalent (DTP-HepB-Hib)

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• Goal
• The goal of public sector is to ensure that high
  quality vaccines are developed in adequate
  capacity and supplied at reasonable prices to
  meet the priority needs of developing countries.
• Current Hypothesis
• The expanded use of combination vaccines in
  developing countries will have a significant
  impact on global supply of the individual
  antigens and programme flexibility.

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Why this study?

• This study should provide some clarity regarding
  the following issues of combination vaccines
• What are the regulatory, supply and programmatic
  issues impacting availability and use of these
  vaccines?
• What are the implications of these issues?
• What can public sector do to maximize the
  opportunity to introduce new antigens via
  combination vaccines in developing countries
  while finding the necessary balance for
  regulation, supply and acceptance?

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Combination Vaccines

• Benefits
• Fewer number of injections
• Fewer syringes used - good for injection safety
  and less waste generation
• Less thiomersal exposure due to fewer total
  injections
• May make the introduction of a new antigen
  transparent

• Drawbacks
• Can limit programme flexibility
• Present regulatory issues
• Impact on supply of traditional vaccines
• One supplier for multiple antigens (supply and
  price) though that will soon change
• Can be more expensive than monovalent options
• Need for cold chain expansion with shift to lower
  dose.

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Vaccines Pre-qualified for Sale by UN Agencies by
Manufacturer

• DC/EE is Developing Country or Emerging Economy
  manufacturers all in purple.
• Industrial country manufacturers and their
  products are in blue.
• All Hep B in this graph is recombinant. There is
  also one pre-qualified plasma derived Hep B
  vaccine manufacturer.

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Regulation and Licensing Statusof Combination
Vaccines
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Issues in Regulation of Combination Vaccines

• Clinical studies
• Interference between antigens in combinations
• Adjuvants and their ability to change the
  immunological characteristics and stability
• Minimum potency levels must be determined
• New reference materials need developing
• Data needed for adverse events analysis

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Licensing Oversight of DTwP based Vaccines EMEA

• EMEA licenses only products that have a market in
  Europe must be re-licensed after five years.
• Recently re-licensed GSKs combinations.
• Spain is now importing significant quantities of
  DTwP-Hep B - hib combination vaccine for use
  which will ease concerns that DTwP based
  combinations are not used in Europe.
• EC undertakes at WHO request, review of product
  file, data and facility. EMEA would not license
  the product, but would delegate authority to the
  relevant NRA all remaining regulatory activities.

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DTwP based combination vaccines

• Supply update
• Antigen allocation production and capacity
• Market characteristics, their effect on demand
  and resulting predictions

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77 of UNICEFs DTwP supply comes from developing
country sources and the amount offered is
narrowly meeting demand. As DTwP is siphoned
for combination, the supply of DTwP for other
programmes could be jeopardized.

• Source Unicef Supply Division

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Availability of Hep B

• Meanwhile the amount of single antigen Hep B
  vaccine is about to reach an all time high with
  the addition of another prequalified Hep B
  manufacturer to the list, and another likely to
  follow soon.
• The only manufacturer making plasma derived is
  also shifting to recombinant Hep B vaccine
  production

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Manufacturer Response to Forecasting Demand

• Source GAVIs Financing Task Force, Forecasting
  Subgroup and UNICEF Supply Division

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Market Characteristics, Determining Acceptance
and Predictions
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Vaccine Costs and Premiumsfor Global Fund
purchase for GAVI
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Determining Acceptance of Combination Vaccines

• If the antigens in the combination are wanted,
  the combination has added value. If the
  combination is affordable, the country is willing
  to pay more to have the vaccines in combination
  form. The premium, if reasonable, is worth the
  benefit (ex. DTwP-HepB).
• However, the simple availability of a combination
  vaccine does not automatically make the product
  of value to the programme (ex. DTwP-HepB-hib in
  Africa or MMR in Japan).

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WHOs Strategic Advisory Group of Experts
Recommendations
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• WHO review the possible combination vaccines and
  the implications on supply, regulation,
  presentation, and price and assist countries to
  assess appropriateness of each combination for
  their national immunization programmes
  consideration of the role of developing country
  production and the implications of sole source
  suppliers should be part of this process

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• WHO, in working with partners, especially vaccine
  manufacturers, provide accurate demand
  forecasting of the various combination vaccines
  (determined by national immunization programme
  managers to be beneficial, programmatically
  feasible, financially sustainable and worth
  introducing if funding were available).

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• WHO place priority on the continued action to
  address and monitor progress with regard to the
  licensing of vaccines in industrialized countries
  for use in developing countries.