Vaccine Product Research & Development efforts at IVR · World Health Organization 4 May 2007 4 7|...

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 ?


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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







important steps



3


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


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


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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


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)


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important steps



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


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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


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


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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







important steps



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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.


� 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).



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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







important steps



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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



� 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.




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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


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 ?


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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


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


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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 ….

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Vaccine Product Research & Development efforts at IVR · World Health Organization 4 May 2007 4 7|...

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