A brief presentation of the market space created by the ongoing ebola epidemic, and projected cost estimates for scale up production vaccine introduction of an ebola vaccine.

1. Estimating EVD vaccine manufacturing costs
and financing requirements for immunization
Dimitrios Gouglas (Dimitrios.Gouglas@fhi.no)
29.10.2014 Estimating EVD vaccine manufacturing costs and financing requirements for immunization 1

2. Developing EVD vaccines in a hurry
• The development, scale up production and implementation of emergency
vaccination to protect against EVD is an international priority
• An EVD vaccine is considered a cost-effective tool to prevent future EVD
epidemics based on our knowledge that, in case of survival, the infection
is followed by natural immunity
• There are promising vaccine candidates in the pipeline that could
potentially become available in the short- to medium- term
• On average, vaccines taken from the preclinical phase require a
development timeline of >10 years and have a market entry probability of
6% (Pronker et al, 2013)
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Estimating EVD vaccine manufacturing costs and financing requirements for immunization
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3. A market space for EVD biopharmaceuticals is being shaped
Applied R&D funding (2008 to July 2014) for EVD drugs and vaccines >US$469m and
NIH basic research funding (2000-2014) <US$1bn, supporting a pipeline of >11 drug
candidates and >8 vaccines
vs
US$500m disbursed
funding and >US$1.8bn
pledged funding in
emergency support to curb
ongoing EVD epidemic
(March - October 12th
2014)
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Estimating EVD vaccine manufacturing costs and financing requirements for immunization
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A ‘market’ space is being shaped, which requires the development of a commonly agreed
framework to estimate product development costs and financing requirements

4. Financing the production and introduction of EVD vaccines
Expected outcomes based on which
support should be provided
•Short- to medium- term: Successful
clinical development and rapid roll-out
of safe and effective vaccines to
tackle the ongoing EVD epidemic
•Short- to medium- term: Access to
vaccines through prioritizing
delivery based on efficiency and
equity (high risk population, which
also will include health workers,
first)
•Medium- to long- term: Improved
and sustained health outcomes
(drop in transmission and
prevalence over time) through a
combination of biomedical and
public health interventions
Market features
•Effective vaccines that meet the
safety and efficacy requirements of
regulators, incuding in West Africa
•Suitable vaccines that supply chain
systems can endure
•Available vaccines to populations
most in need
•Secure vaccine supply through
manufacturing scale-up and/or
supplier diversification
•Demand creation through reliable
and predictable financing
•Affordable pricing to ensure donor
value-for-money and endemic
countries’ ability to self-finance the
vaccines
Bottlenecks with developing and
rolling out vaccines
•Clinical testing of prioritized
vaccines
•Risk of failure and lack of back-up
options
•Data requirements for vulnerable
groups
•Long time-to-market due to
inability to evaluate vaccine
efficacy adequately or regulatory
/political barriers
•Manufacturing
•Limited vaccine production
capacity (including sterile filling)
and lack of incentives for
emergency vaccine production
•IP licensing and speed of tech
transfers for scaling up production
•Limited partnerships for scale-up
production and manufacturing
•Supply chain
•Optimizing formulations,packaging
and storage conditions
•Speed of procurement, shipment
and delivery
•Vaccine uptake
•Vaccine introduction costs
•Stock requirements and stock
management capacities
•Lack of adherence and political
buy-in
•Awareness raising and reputation
protection of roll-out efforts
Key interventions
•Accelerating R&D and
manufacturing efforts
•Provide direct funding for vaccine
trials and manufacturing, based on
cost of production modelling,
cost+ pricing and appropriate IP
licensing
•Identify back-up candidates in case
of poor safety and efficacy results
of prioritized vaccines.
•Establish a a coordination
mechanism to drive the process
forward, building on lessons learnt
from other collaborative initiatives
•Fast-tracking regulatory approval
•Work with national regulators
without jeopardizing ethical and
clinical standards.
•Assist vaccine developers with
dossier submissions and
negotiations with regulators
•Planning vaccine procurement and
delivery
•Plan procurement and delivery;
initiate demand forecasting and
vaccine introduction costing
•Supporting vaccine uptake
•Build a robust awareness raising
and communication strategy
•Liaise with endemic countries to
determine vaccine needs and
introduction capacities
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5. Potential market for EVD vaccines
• Assume that vaccines will be
limited to the three endemic
countries: Sierra Leone,
Guinea and Liberia (19.8
million) (Basic Scenario)
• Assume that a ring
vaccination strategy will be
adopted to additionally
include: Guinea-Bissau,
Senegal, Mali, Ivory Coast
(53.3 million) (Intermediate,
Ring Vaccination Scenario)
• Assume vaccination
coverage >50% of total
population
• Assume a reactive campaign
strategy is adopted that is
not followed by routine
immunization
Preliminary estimates of
the potential market: ~10 to
37 million
Market drivers
• Scope of vaccination
strategies based on choice
of design and time span of
immunization efforts (e.g.
routine vs catch-up
campaign immunization)
• Diversity of vaccination
schedules based on different
age and risk cohorts
• Product profile
requirements (e.g. number
of doses to achieve full
immunization; vial
packaging; heat stability and
cold chain requirements,
etc.)
• Potential market can reach
140 to 290 million if all
countries at risk of EVD
introduce EVD vaccines in
their routine immunization
programmes with 50%
coverage targets
• Demand uncertainties and
supply security can also
impact market size
Market size will depend on
the appropriate strategy
selected for controlling EVD
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Estimating EVD vaccine manufacturing costs and financing requirements for immunization
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6. Evidence on costs of production
Small scale production for clinical phase I and II trials (N=200-300) in African country settings can
cost US$1-2m per country (NIPH estimates from past vaccine trials in African countries)
Complexity of vaccine technology & bulk
production capacity (Smith, 2011)
•Flu vaccine – 60m egg-based doses for US$600m
vs US$150m for 100m mammalian cell culture
based doses vs 75m insect cell-culture based
doses for US$225m (Robinson et al, 2008)
The closer to full capacity, the lower the cost per dose
•From ~ US$1.75 to ~ US$0.70 per dose as dengue
vaccine production increases from 15m to 60m doses
per year (Mahoney et al, 2012)
•From US$20 to US$0.10 per dose as HepB vaccine
production increased from small Q to 20m doses per
year (Mahoney, 1990)
Other cost drivers include:
•time-span, operational and regulatory requirements of
clinical trials
•361m (Di Masi, 2007); 192m Rotarix & 206m RotaTeq
(Light et al, 2009)
•Location; raw materials required; equipment; people
(Datla, 2012)
Bulk production and fill-finish for GAVI vaccines requires on average cash flows of US$50m to US$500m, with ~
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Estimating EVD vaccine manufacturing costs and financing requirements for immunization
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60% fixed costs; 25% semi-fixed (per-batch) costs; and 15%variable costs (Datla, 2012)

7. Projected EVD vaccine production cost
• An extremely simplified, crude estimation, based on the following assumptions:
(1) The manufacturing process of an EVD vaccine is relatively similar to that of a hypothetical dengue
vaccine, where it has been demonstrated that cost of manufacturing can reach US$1.75 for 15m
dose production per year.
(2) Production cost per dose remains steady as production volume increases.
(3) Under a cost+ pricing agreement, total cost of production cannot exceed US$2 per dose – a
reasonable cost ceiling for affordable pricing in low income country settings;
(4) Costs of R&D and marketing are excluded;
(5) Scale up production can be accomplished in modestly sized process equipment, where
production capacity is already in place, including sterile filling and GMP;
(6) Technology transfer or other IP licensing costs are excluded;
(7) Registration dossier submission costs are excluded;
(8) Additional laboratory and clinical studies required by stringent regulatory authorities or to satisfy
alternative storage temperatures or formulations are excluded;
(9) Costs are not capitalized
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Estimating EVD vaccine manufacturing costs and financing requirements for immunization
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INTERMEDIATE SCENARIO: ~ 37m doses x US$2 per dose = ~ US$74m
BASIC SCENARIO: 10m doses x US$2 per dose = US$20m

8. Projected EVD vaccine introduction costs (1)
Simplified,
crude
estimation,
based on
following
assumptions:
Target
coverage
<50%
Only direct
costs of
purchase and
exclude
procurement
and freight
Costs at high end of previous
meningococcal vaccine reactive
campaigns and MenAfriVac™
estimates:
•2009 Niger and Nigeria:
US$15m for 7m people
•2007 Burkina Faso : US$3.5m
for 4m people
•MenAfriVac: US$12.-15m for
country of 12m
BASIC SCENARIO: 10m doses x US$2.14 vaccine introduction cost per capita = ~ US$21.4m
INTERMEDIATE SCENARIO: ~ 37m doses x US$2.14 vaccine introduction cost per capita = ~ US$78.6m
• Immunization financing will depend on coverage thresholds and scale of the
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Estimating EVD vaccine manufacturing costs and financing requirements for immunization
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campaigns, sequence of targeting population cohorts, price of the vaccine
and supply chain capacities

9. Projected EVD vaccine introduction costs (2)
If channeled through GAVI Alliance (considered the safest and most cost-efficient
channel), full vaccine introduction costs could exceed US$38.4m
(basic scenario) and US$139.1m(intermediate scenario)
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assuming these additional costs
• Freight (shipment and delivery) costs similar to the Yellow Fever Vaccine that also has significant cold
chain requirements:
– ~25% under basic scenario (based on 2012 actual freight costs for YF vaccines through GAVI/UNICEF
SD: 33% Sierra Leone; 22% Liberia; 19% Guinea)
– ~23% under intermediate scenario (in addition to the three endemic countries, also based on 2012
actual freight costs for YF vaccine through GAVI / UNICEF SD for Guinea-Bissau (35%) and Mali
(25%); based on 2012 lowest actual freight cost of 13% for YF vaccine through GAVI / UNICEF SD in
the case of Senegal and Cote D’Ivoire)
• Cost of safety boxes and syringes 5% (based on ceiling set by GAVI in vaccine co-financing requirements
for low income countries)
• Wastage rate of 10% (crude estimate based on GAVI weighted average pricing estimates)
• Buffer stock requirement 25% ( based on WHO minimum stock requirement for routine vaccines in GAVI
countries)
• Procurement services fee 4% (based on UNICEF SD average procurement fee)
• Procurement buffer 10% (based on UNICEF SD financial security buffer requirement)

10. Financing requirements for the production and
introduction of EVD vaccines
29.10.2014
BASIC SCENARIO: ~ US$ 41.4 – 58.4m
• Low end: US$20m (production) +
US$21.4m (introduction)
• High end: US$20m (production) +
US$38.4m (introduction)
INTERMEDIATE SCENARIO: ~ US$ 152.6 – 213.1m
• Low end: US$74m (production) + US$78.6m
(introduction)
• High end: US$74m (production) + US$139.1m
(introduction)
Estimating EVD vaccine manufacturing costs and financing requirements for immunization
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• More robust estimates of financing needs require an in-depth analysis of scale up
production, vaccine introduction and cold-chain capacity strengthening costs, with
data on costs and timeframes to be obtained directly from EVD vaccine developers