Coordination of Vaccine R&D The WHO/Initiative for Vaccine Research approach

1. Coordination of Vaccine R&DThe WHO/Initiative for Vaccine Research approach Marie-Paule Kieny Initiative for Vaccine Research

2. Presentation outline • Why vaccine R&D in WHO? • Example of a comprehensive IVR R&D project: the example of influenza vaccine • Selected WHO activities with direct relevance to influenza vaccine R&D: 2007 – 2008 • WHO influenza vaccine technology transfer project

3. WHO mandate for R&D The core functions of WHO guide the work of the Secretariat, influence approaches for achieving the strategic objectives, and provide a framework for assuring consistency and output at global, regional and country levels. The second of the 6 core functions concentrates on research: "shaping the research agenda, and stimulating the generation, dissemination and application of valuable knowledge".

4. The need for increased investment in vaccine research • Vaccines are the cornerstone of the fight against communicable diseases • However, infectious diseases are still responsible for nearly 30% of all deaths worldwide representing over 15 million people of whom 6.7 million are children –every year mostly in low and middle income countries. • Approx. an additional 1.4 million deaths in children under 5 could be averted if available vaccines were applied universally. Large scale implementation of pneumo and rotavirus vaccines could avert an additional 1.1 million death in this age group

5. New landscape in Vaccine R&D • A number of new vaccines have been developed & licensed in recent years • Increased awareness of health issues in the developing world has led to the emergence of several initiatives & partnerships • BUT… for a number of diseases there is still a lack of needed leadership, funding & supportive implementation to bring a vaccine to the market

6. How does IVR supports the vaccine research pipeline ? By using a three-pronged approach: • Management of knowledge & provision of guidance & advocacy through effective partnerships to accelerate innovation; • Support to research and product development; • Implementation research, and development of tools to support evidence-based recommendations.

7. Influenza vaccine R&D coordination at WHO/IVR

8. Selected WHO activities with direct relevance to influenza vaccine R&D: 2007 – 2008 • 3rd WHO Meeting on Influenza Vaccines that Induce Broad-spectrum and Long-lasting Immune Responses, December 2007 www.who.int/vaccine_research/diseases/influenza/meeting_071203/en/index.html • 3rd WHO Meeting on Evaluation of Pandemic Influenza Prototype Vaccines in Clinical Trials, February 2007 www.who.int/vaccine_research/diseases/influenza/meeting_150207/en/index.html • 4th WHO Meeting on Evaluation of Pandemic Influenza Prototype Vaccines in Clinical Trials, February 2008 www.who.int/vaccine_research/diseases/influenza/meeting_140208/en/index.html • Dissemination of information on results of Clinical Trials of Pandemic Influenza Prototype Vaccines www.who.int/vaccine_research/diseases/influenza/flu_trials_tables/en/index.html (last update August 2008)

9. Selected WHO activities with direct relevance to influenza vaccine R&D: 2007 – 2008 (continued) • Review of Production Technologies for Influenza Virus Vaccines, and their Suitability for Deployment in Developing Countries for Influenza Pandemic Preparedness www.who.int/vaccine_research/diseases/influenza/Flu_vacc_manuf_tech_report.pdf • Use of Cell Lines for the Production of Influenza Virus Vaccines: An Appraisal of Technical, Manufacturing and Regulatory Considerations www.who.int/vaccine_research/diseases/influenza/WHO_Flu_Cell_Substrate_Version3.pdf • Mapping of Intellectual Property Related to the Production of Pandemic Influenza Vaccines www.who.int/vaccine_research/diseases/influenza/Mapping_Intellectual_Property_Pandemic_Influenza_Vaccines.pdf • Consultation on Options for Live Attenuated Influenza Vaccine in the Control of Epidemic and Pandemic Influenza, June 2007 www.who.int/vaccine_research/diseases/influenza/meeting_120707/en/index.html

10. Formulation of the Global Pandemic Influenza Action Plan to increase vaccine supply (GAP 2006) Developed through extensive consultation Goal and specific objectives: • Developing enough pandemic vaccine to immunize the world's population (6.7 billion people in 6-9 months) • "by increasing the supply of a pandemic vaccine and thereby reducing the gap between the potential vaccine demand and supply anticipated during an influenza pandemic" • Increase use of seasonal vaccine to drive market & production capacity • Expand vaccine production capacity • Encourage further research and development

11. WHO Influenza vaccine technology transfer project • Why did we undertake the project? • WHA resolution • Most influenza vaccine production capacity resides in North America and Europe • The increase of potential pandemic vaccine supply is a global public health priority • Are we in well positioned to carry out this task? It fits IVR's "mandate": • knowledge management and facilitator of development • linking with normative and regulatory aspects • linking with team coordinating flu pandemic preparedness (GIP) • assisting developing countries • Howare we doing it? concepts, process, lessons learnt

12. Technologies chosen by the six WHO grantees selected through an independent selection process to build in-country Influenza vaccine production capacity IIV Egg 1000 IIV Tissue Culture New cell line IVAC, Vietnam IIV Tissue Culture Established cell line 100 BIRMEX, Mexico Investment required (US$ millions) BioFarma, Indonesia Butantan, Brazil 10 - Serum Institute of India LAIV Egg 1 - Thai GPO 0 2 4 6 8 10 12 Time required to establish seasonal vaccine production (years)

13. Achievements as of January 2009 • Significant progress from most developing country vaccine manufacturers during the first year of the grant • Acknowledgement by the WHA and the IGM • Establishment of a network of experts to facilitate & support the process • Timely implementation with strong follow-up from WHO • Training • Technical support • Monitoring • Additional vaccine manufacturers have applied (e.g. Egypt, Iran, Argentina). Selection of new projects is pending.

14. Challenges • Finding a technology transfer partner is very difficult • Industrialised country vaccine manufacturers have limited interest • Butantan (Brazil): had technology transferred from Sanofi • BioFarma (Indonesia): is receiving tech transfer from Biken • Limited human resources at new manufacturer site • Need an experienced team for SOPs, Batch Process Records, etc… A possible solution: to create a "technology hub" to serve as technology provider

15. A "technology hub" to serve as technology provider • A technology platform for transferring a single robust production process with relevant documentation (SOPs, Batch Process Records, validation procedures, analytical methods and release criteria) • A technology package transferable to any interested developing country vaccine manufacturers, upon requests (and possibly fees), without IPR hurdles • Selected technology: Inactivated whole virion Influenza Vaccine produced in eggs

16. Lessons learnt … • Establishing a "technology hub" represents an interesting potential: • for expansion to multiple interested recipients • a single technology & • it offers possibilities for sustainability, for example through fees contributed by the "tech-transferred" vaccine producers • The "hub" concept can be applied to other areas and /or technologies.