Transcript Why this study?

New Vaccine Supply and Financing:
A Case Study of Combination
Vaccines in Developing Countries
Viral Hepatitis Prevention Board Meeting
Malta
October 22-23, 2001
Global status of countries using HepB vaccine in their
national immunization system, 2001
Routine HepB implementation status
No
Yes
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.
August 2001
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 (DTPHepB) or pentavalent (DTP-HepB-Hib)
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.
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
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
Vaccines Pre-qualified for Sale by
UN Agencies by Manufacturer
DTwP HepB hib DTwP- HepB DTwP- HepB + hib (lyo) measles MR MMR
Aventis Pasteur
Biken, Japan
Bio Farma, Indonesia
Chiron, Germany & Italy
CSL, Australia
Glaxo Smith Kline, Belgium
GreenCross Vaccine, Korea
Lucky Goldstar, Korea
Merck and Co.
Serum Institute of India
Swiss Serum Institute
3 DC/EE in process
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.
Regulation and Licensing Status
of Combination Vaccines
Base vaccine
Specific Combination
Licensing Status
DTwP
DTwP-hep B
DTwP-Hib
DTwP-hep B-Hib
Europe primarily for developing country market
Europe primarily for developing country market
Europe primarily for developing country market
DTaP
DTaP-hep B
DTaP-Hib
DTaP-hep B-Hib
DTaP-hep B-Hib-IPV
Europe and U.S.
Europe
Europe
Europe
Measles
MMR
MR
MM
Europe and U.S. and many countries
Europe and U.S. and many countries
Europe, U.S., Russia and many countries
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
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 GSK’s 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
DTwP based combination
vaccines
• Supply update
• Antigen allocation: production and
capacity
• Market characteristics, their effect
on demand and resulting
predictions
77% of UNICEF’s 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.
600
500
400
Availability
300
Demand
200
100
0
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
Millions of Doses
DTwP
Year
Source: Unicef Supply Division
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
Manufacturer Response to
Forecasting Demand
140
120
100
80
60
40
20
0
DTwP-hep B-Hib
Estimated demand 2001-2003
DTwP-hep B
Response to UNICEF RFP
Source: GAVI’s Financing Task Force, Forecasting Subgroup and UNICEF
Supply Division
# of doses (in millions)
Antigen Re-allocation: Review of One
Producer's Response
140
120
100
80
60
40
20
0
DTwP-hep B-Hib
DTwP-hep B
Estimated demand 2001-2003
Response to UNICEF RFP
Effect of antigen reallocation
Market Characteristics, Determining
Acceptance and Predictions
Market Characteristics
Africa GAVI market
Latin America
Financial condition
Poor
middle income
General programmatic
condition
Weak
strong
Programmatic flexibility
Ability to make decision to
change usage
Local vaccine production of
DTwP, hep B, or Hib
Hib disease burden
hep B disease burden
Prediction
Can choose, more easily, to be
flexible
Limited flexibility
Generally the regulatory body is
not qualified to make alternate
usage decisions
Regulatory body is qualified to make
usage decisions
None
High but other more pressing
problems of concern
some
High burden with several studies
already performed
Very high
High uptake of DTwP-hep B;
Not likely to buy anything for
which there is not a great need.
Lower (priority for Hib above hep B)
High uptake of DTwP-Hib;
Probably willing to buy combos with
inexpensive extras (like hep B).
Vaccine Costs and Premiums
for Global Fund purchase for
GAVI
Vaccine
Vial size
DTwP
hep B
Hib (liq)
DTwP- hep B
10 dose
10 dose
1 dose
10 dose
DTwP - Hib (liq)
1 dose
DTwP-hep B-Hib (liq)
2 dose
Cost of vaccine per
dose in 2001 or
soonest available
0.078
0.32
2.70
1.10
3.00
from 2002
3.50
Premium from 2001-03
and expected trend
N/A
N/A
N/A
+ 0.70 to
+ 0.50 decreasing
0
steady
+ 26 to
- 0.14 decreasing
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).
WHO’s Strategic Advisory
Group of Experts
Recommendations
 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;
 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).
 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.