Post on 02-Feb-2020
World Health Organization 4 May 2007
1
Vaccine Product Research & Development efforts at IVR
Initiative for Vaccine Research
Annex 4
Product Research & Development at IVR | April 20072 |
ContentsContents
� Why is crucial for IVR to contribute to Product Research and Development ?
� What are the comparative advantages of IVR in this area ?
� What have we achieved in the past years ?
� What have we learnt ?
� Where are our efforts leading us to ?
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 20073 |
Why is it crucial for IVR to contribute to
Product Research & Development ?Why is it crucial for IVR to contribute to
Product Research & Development ?
� Support for key products that lack R&D investment and leadership
�Catalyze R&D processes by participating in
important steps
� Promote and nurture collaborations with key stakeholders
Product Research & Development at IVR | April 20074 |
Why is it crucial for IVR to contribute to
Product Research & Development ?Why is it crucial for IVR to contribute to
Product Research & Development ?
� Support for key products that lack R&D investment and leadership
�Catalyze R&D processes by participating in
important steps
� Promote and nurture collaborations with key stakeholders
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 20075 |
Measles Aerosol ProjectMeasles Aerosol Project
� Mobilized a network of supportfor the MAP:
– effective partnership with CDC & ARC
– global access framework in place – MoUs with SIIL & 3 device companies
– nearly 200 experts involved in the project
– collaborations with SVI, ISAM, AktivDry.
� Foresaw the potential of a new route of administration for measles & other vaccines:
– mobilized support from the BMGF & others
– generated the critical "virtual team"
– led a systematic review of evidence
– offered an alternative safer &, easier to use method
Product Research & Development at IVR | April 20076 |
Measles Aerosol ProjectMeasles Aerosol Project
� Generating additional knowledge:
– regulatory pathway for aerosol
vaccines
– usability criteria for device
selection
– optimal SOPs for PRNT
– method to assess vaccine
potency retention
– contribution to development of
other formulations
� Successfully implementing a development plan with limited financial resources:
– pre-clinical studies completed
– phase 1 studies ongoing-preliminary data suggest good safety & immunogenicity.
– plans to start PIVOTAL trial in early 2008
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 20077 |
LICENSUREInitially in India
Measles Aerosol Project Clinical Trials & device usabilityMeasles Aerosol Project Clinical Trials & device usability
No go: Safety1 2 No go: Safety & Immunogenicity
India(180 volunteers 1-35 yo)
Phase I
India ( ~ 3500 children
9 mo & 4-6 yo)
Pivotal trial
12
30 days dataTotal f-up= 365 d
Year 4 Year 5 Year 6 …..
Demonstration studies Post-marketing studies
Introduction …
90 days dataTotal f-up= 365 d
Usability /logistics criteria & field testing
Optimal device design
Product Research & Development at IVR | April 20078 |
Geometric mean titres by site and day of bleed
0
5000
10000
15000
20000
25000
day-30 day28 day90
GMT IU/mL
Chennai
Kolkatta
Pune
All increase day 0 to 28.
Day 28 to 90 depends on site with increase in Chennai, decrease in Kolkata.
Day 0 and 28 don’t differ by site but day 90 do.
Preliminary results- Phase I trial, India 17-35 yo healthy measles immune, 3 sites, 20 subjects per site
Fold rise
(95% CI)
Fold change
Day -30 mIU/mL
<=0.25
0.26 to 0.99
1 to 3.99
>=4 (%)
<=2000 5.0 (2.9-8.7) 0 1 8 11 (55%)
2001-6000 2.3 (1.5-3.6) 0 2 13 4 (21%)
>6000 0.9 (0.7-1.2) 0 13 8 0 (0%)
Overall 2.2 (1.6-2.9) 0 16 29 15 (25%)
Adjusting for day 0 when comparing sites by day 28 gives
no difference by sites (p=0.14) (Unadjusted also no
difference p=0.09)
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 20079 |
Why is it crucial for IVR to contribute to
Product Research & Development ?Why is it crucial for IVR to contribute to
Product Research & Development ?
� Support for key products that lack R&D investment and leadership
�Catalyze R&D processes by participating in
important steps
� Promote and nurture collaborations with key stakeholders
Product Research & Development at IVR | April 200710 |
Meningitis Vaccine ProjectMeningitis Vaccine Project
� Laid the ground for a tailored product profile & innovative product development design:
– fostered an analysis of the
costs to develop the vaccine
– sought countries & experts
input on optimal target price
– envisioned the need for an
alternate development strategy
� suggested a tailored vaccine could be produced for less than $US 0.50 per dose
� Initiated efforts towards a new vaccine to fight epidemic meningitis & mobilized partners:
– brought the need for a new vaccine to the attention of partners
– mobilized the key funding resources to launch the MVP
N0 1000 200 0 Kilometers
Average annual rates per 100,000
0 - 2.93 - 9.910 - 24.925 - 120
Meningitis belt 4.5
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 200711 |
Meningitis Vaccine ProjectMeningitis Vaccine Project
� Bridging across partners to establish a sound development & regulatory plan:
– phase I successfully conducted in India
– phase II underway in two key sites in Africa
– advanced planning for Phase II/III studies in 4 key African sites, 1 Indian site
– guidelines on technical specifications for QC & production of Men A conj
� Ensuring a harmonious & sustainable capacity buildingand access strategy at all levels:
– strengthening regulatory
oversight of African countries
– inter-site collaboration
– triggering conduct of large
carriage studies across the
African belt
– enriching discussion on
choice of schedules
Product Research & Development at IVR | April 200712 |
MVP Vaccine DevelopmentCountry Level ActivitiesMVP Vaccine DevelopmentCountry Level Activities
TechnologyDiscovery & Transfer
Pre-clinical Development
Clinical Development
Licensure
Demonstration
Introduction
DCGI
Submission
June 2008
Process Development
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 200713 |
MVP Phase I – Safety, Immunogenicity &Immune Persistence ResultsMVP Phase I – Safety, Immunogenicity &Immune Persistence Results
� SBA persisted at significantly
higher levels for the PsA-TT than
for the polysaccharide group
1
10
100
1000
PsA-TT PsA/C TT
Vaccine
Group A-specific IgG GMC (95% CI)
Baseline
4 week
� The group A conjugate vaccine, PsA-TT, was safe
and immunogenic in Indian adults
� PsA-TT induced higher SBA and ELISA Ab levels than the licensed PsA/C polysaccharide vaccine, with significant differences between the Group A- GMCs
� PsA-TT boosts tetanus responses
Product Research & Development at IVR | April 200714 |
Why is it crucial for IVR to contribute to
Product Research & Development ?Why is it crucial for IVR to contribute to
Product Research & Development ?
� Support for key products that lack R&D investment and leadership
�Catalyze R&D processes by participating in
important steps
� Promote and nurture collaborations with key stakeholders
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 200715 |
Global Adjuvant Development InitiativeGlobal Adjuvant Development Initiative
Serving as a hub for this activity:
– links to public-sector vaccine development groups: provides pipeline for use of adjuvants
– no ties to specific products: neutral broker
– in-house expertise on adjuvant research, development and production
� Identified access to adjuvantsas a major bottleneck to development of new vaccines:
– presented the challenge to major vaccine-development funding agencies.
– proposed structure and mechanism for public-sector adjuvant development initiative.
Product Research & Development at IVR | April 200716 |
� Promote access to critical information:
- organized conference series
on adjuvants and
formulations
- established database of
adjuvants in clinical trials
- provide advice to vaccine
developer partners on
selection of adjuvants and
� Created the Global Adjuvant Development Initiative:
– partnership with IDRI on
downstream development
– project with WellcomeTrust on upstream development
– network of public-sector adjuvant users (AdjuNet).
Global Adjuvant Development InitiativeGlobal Adjuvant Development Initiative
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 200717 |
Global Adjuvant Development InitiativeGlobal Adjuvant Development Initiative
Clinical trials
Vaccine development
WHO WHO WHO WHO ---- IVRIVRIVRIVRCoordination between
activities
Dissemination
ADJUNET
MVI
EMVI
AERAS
IAVI
TBVAC
PATH
NIAID
NVI
...
IDRIIDRI
WHO WHO collaborating collaborating centercenter on on adjuvantsadjuvants
Access and supply of licensed
DOWNSTREAM GMP products
Formulation resource center
India
Wellcome/WHO adjuvant development center
Access midstream and new
immunostimulants
Product Research & Development at IVR | April 200718 |
Why is it crucial for IVR to contribute to
Product Research & Development ?Why is it crucial for IVR to contribute to
Product Research & Development ?
� Support for key products that lack R&D investment and leadership
�Catalyze R&D processes by participating in
important steps
� Promote and nurture collaborations with key stakeholders
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 200719 |
Facilitating technology transfer:
- seeking inputs from country
level.
- support by all WHO teams
involved in pandemic
preparedness and response
- identifying appropriate
production technology to suit
national preparedness plans
- canvassing current in-house
expertise on influenza vaccine
research, development,
production, and delivery.
� Addressing a WHA resolution, developed the Global pandemic influenza Action Plan to increase vaccine supply (GAP):
-strategies to increase in
country supply of
influenza pandemic
vaccines
- in collaboration with
governments, industry
and, NGOs
Pandemic Influenza Vaccine capacity building
Pandemic Influenza Vaccine capacity building
Product Research & Development at IVR | April 200720 |
� Guiding the establishment of critical partnerships
– guidance document:
"Technologies for pandemic
influenza vaccine production"
– facilitating partnerships with
IP and technology holders
– coordinating reviews on
clinical development of
pandemic vaccines and, on
broad-spectrum influenza
vaccines
� Increasing productioncapacity
– management of large
multinational grants for
developing-country
vaccine production
capacity building
– six grants to be awarded
to developing country
producers in 3 regions.
Pandemic Influenza Vaccine capacity building
Pandemic Influenza Vaccine capacity building
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 200721 |
Modelling the potential production yield of two influenza vaccines in a fixed size production facility
Modelling the potential production yield of two influenza vaccines in a fixed size production facility
0
100
200
300
400
500
600
700
1 2 3 4 5 6 7 8 9 10 11 12
Weeks After Commencing Production
Cummulative Doses (Millions)
PIIV LAIV
No need for syringes and needles.
Minimal health-care-worker burden
Need for availability of syringes and needles.
Requires qualified health-care-workers
Live attenuated
Inactivated
Product Research & Development at IVR | April 200722 |
Establishment of large-scale seasonal influenza vaccine production capacity: Timeline and cost
Establishment of large-scale seasonal influenza vaccine production capacity: Timeline and cost
1000
2 10864
0
12
10
1
100
Investment required
(US$ millions)
LAIVEgg
IIV
Tissue CultureEstablished cell line
IIV
Egg
Time required to establish seasonal vaccine production (years)
IIV
Tissue CultureNew cell line
SII
Butantan, IVAC
Biofarma ? Thai MOH?
Thai MOH ?
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 200723 |
What have we learnt ?What have we learnt ?
� IVR is in a privileged position to act as a hub for partnerships /collaborations in RPD.
�WHO's mandate permits better understanding of country needs & priorities.
�WHO outreach promotes sustainable capacity building.
�Despite perceived large bureaucracy, IVR had efficiently led the PR&D processes.
� IVR team comprises a broad expertise
⌧ Some reference/specialized
groups may be better positioned
to implement some of the more
upstream activities.
⌧WHO need to streamline some
of the contractual processes.
⌧ In some circumstances, it is
more cost effective to use
specialized resources already
located with our partners
Product Research & Development at IVR | April 200724 |
Where are our efforts leading us to ?Where are our efforts leading us to ?
� We need to finalize the projects that are ongoing.
� We must capitalize on lessons learnt and use them to
develop broad guidance/tools
� We should be vigilant and identify other "orphan" products
that may require our involvement
� We must, in a continuous and proactive way help partners
to link efficiently with other teams of WHO and our partners
World Health Organization 4 May 2007
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Product Research & Development at IVR | April 200725 |
We understand the value of effective partnerships !!!!
We understand the value of effective partnerships !!!!
Building partnerships is critical
They help to ensure that we effectively nurture vaccine R&D steps with vaccine introduction strategies and, sustainability approaches at early stages in the development process ….