Workshop on Technology TransferWHO HQ

Geneva, November 30th – December 1st, 2010.

ARVAC project: the “Enabling Platform” model

Jean-Marie Préaud

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PATH’s vaccine development projects• Pneumococcal

disease

• Diarrheal disease

• Rotavirus

• Enterotoxigenic E. coli and Shigella

• Influenza

• Malaria

• Meningococcal disease

• JapaneseEncephalitis

Ph

oto

: PA

TH

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History - Strategy

• 2006: Grant from BMGF to develop Rotavirus Vaccines

• 2006: « Advancing Rotavirus VACcines » (ARVAC) project islaunched:

• 2007: Bill Wainright (Scientific Advisor) proposed the innovative concept of « Enabling Platform »:

• This toolbox of technologies, training, methodologies, and material is designed to meet common needs among emerging vaccine manufacturers and maximize global availability of rotavirus vaccines.

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Organizational model: the « Enabling Platform »

• The “Enabling Platform” is a pool of (1) organizations, (2) consultants and (3) PATH experts with specific expertise to assist the four BRV manufacturers:

• Butantan,

• Shantha,

• Serum Institute of India and

• Wuhan Institute of Biological Products.

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Organizations

Assays used in ClinicCMC

Process DevelopmentIDT

FormulationARIDIS + PATH Technology Solutions

Reagents for characterizationMCRI

QC testing on Vero Cells Banks and Virus

Seeds

CRL + Texcell

Qualified Vero CellsATCC

Assays; sCMV

Sequencing, detection of PCV

NIH (Dr Kapikian)

NIH (Dr Patton)

ContributionsOrganizations

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Consultants

ExpertiseConsultants

Statistics, clinical design R. Kohberger

Clinical assaysR. Ward, M. McNeal

Regulatory, DCGI and WHO PQG. Spizzamiglio

Clinical developmentD. West

Validation of QC assays

GMP, QMS

A. Goldenthal, N. Harjee

Pre-clinical, tox studiesE. Rommel

Process, manufacture and QCW. Wainright

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PATH experts

Project ManagementG. Thiry, M. Socquet (Ferney)

PackagingOptimize (Ferney). M. Zaffran, S.

Zipursky

FormulationD. Chen, M. Lal (Technical Solutions-

Seattle)

Process and ManufacturingJM Preaud (Ferney)

Clinical, immunology, vaccine

development

J. Boslego, D. Steele, J. Flores, K.

Lewis (DC –Seattle)

G. Thiry (Director ARVAC)

ExpertisePATH experts

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Rotavirus partnerships

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On going activities (1) : Process development at IDT

• IDT Biologika, Dessau, Germany

• Objective: IDT-Biologika is developing a process for production in Vero fixed on micro-carriers, in bioreactor, and compares this technology with flasks.

• The goal of this work is to optimize and to compare the mostefficient upstream technologies in terms of virus replication

capacity, costs, aseptic procedures and scalability.

• Manufacturers received the reports

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On going activities (2) : QC testing at CRL and TEXCELL

• Charles River Laboratories (USA) and Texcell (France)

• Objective: CRL provided QC testing and characterization of

material on Vero cell banks, seeds and lots.

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On going activities (3): Production of reagents atMCRI

• Murdoch Children Research Institute

• Production of a series of reagents for the testing of BRV Rota vaccines:

• 1. Monoclonal antibodies (directed to genotype G1, G2, G3, G4 and G9)

• 2. Reference standards (Bovine reassortant viruses)

• 3. Polyclonal antisera

• 4. Wildtype virus stocks – parental strains

• Achievements: material produced and sent to manufacturers

• Standardization of Immuno Fluorescence Assay test

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On going activities (4): Formulation

• ARIDIS and PATH Technology Solutions

• Objective: development of full liquid all-in-one formulation

• Achievements: Aridis developed liquid formulations with the antacid buffer mixed with the rotavirus.

• Formulations were presented to manufacturers at the Annual BRV Meeting (Bangkok, June 09).

• Technology Solutions Lab ( TS, PATH Seattle) further developed these formulations and blending procedure. TS met with manufacturers for technical assistance in the preparation of the liquid formulation .

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On going activities (5): Clinical assays

• CMC Vellore

• Objective: Production of reagents for clinical assays, training, QC

• Achievements: Production of reagents completed, Training on going.

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Support by PATH

• Product Development

• Design of new GMP pilot facilities for cell cultivation area and viral area for Rota vaccine development

• Training and implementation of Quality Management Systems, Good Manufacturing Practices, EnvironmentalMonitoring Program

• Qualification of facilities and equipment

• Technical support for process development

• Technical support for formulation of full liquid vaccine

• Technical support for packaging and delivery systems

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Support by PATH

• Pre-clinic, Clinical and Regulatory Development

• Support in preparation of Clinical Development Plan

• Design of pre-clinical package

• Preparation of tox studies

• Follow up of tox studies

• Review of protocols including statistics

• Validation of clinical assays

• Design of Phase 3 and operations

• Support in preparation of files for Phase 1

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How to transfer know-how

• 4 manufacturers are active in the development of BRV vaccines: Butantan, Serum Institute of India, Shantha, Wuhan Institute of Biological Product and all have specific needs in terms of vaccine development

• PATH provides know-how through : Annual BRV ReviewMeetings, periodic visits to Manufacturers, ad hoc support according to specific needs

• PATH provides general documentation and assistance in termsof vaccine development, testing, formulation, packaging, clinicaldevelopment, regulatory

• For the benefit of all manufacturers in terms of time saving and coherence of BRV network

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Conclusions

• PATH ARVAC has a large experience in the development of Rotavirus vaccines and provides technical support and monitoring through internally expertise, through a network of consultants and through a network of sub contractors.

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Annual BRV Meeting – Kuala Lumpur, June 2010

Thank you !

Jean-Marie PréaudSenior Technical Officer jpreaud@path.org

0033 450 280 8350033 673 790 437

www.path.org