The MenAfrivac Experience A Successful Approach. Dr Bernard FRITZELL BFL conseils France

Transcription

1 The MenAfrivac Experience A Successful Approach Dr Bernard FRITZELL BFL conseils France 1

2 Ministers of Health and Interior from 16 African countries recognized epidemic meningitis as a high priority

3 Development of Meninigitis Vaccine Project (MVP) - History Renewed interest in meningococcal conjugate vaccines at WHO after the epidemic EVA (Epidemic Vaccines for Africa) project established at WHO (Dr. Luis Jodar) Major disparity in vaccine development and availability for diseases predominant in developing countries as opposed to those affecting developed countries Three MenC conjugate vaccines in 2000 in response to the increasing rates of group C infection in the UK in the 1990s ( cases in the decade) No plan to develop a MenA conjugate whereas more than cases reported in the meningitis belt in the same decade, despite the use of polysaccharide vaccine 3

4 Development of MVP - History Classical push strategy from the public sector was insufficient Independent assessment commissioned by WHO (2000) Development of a business model for A or A/C meningococcal conjugate vaccines Monovalent mena conjugate preferred because it is largely predominant serogroup in the African meningitis belt and would the greatest public health impact. Simpler and faster to develop. Production of a mena conjugate at a cost of less than 0.50 US$ deemed feasible ++ Collaborative initiative between WHO and PATH to support the Meningitis vaccine project (MVP) $ 70 million grant from Bill & Melinda Gates foundation (2001) 4

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6 MenA conjugate vaccine development Could not reach after in-depth discussions with major vaccine manufacturers an agreement toward a collaboration to produce an affordable MenA vaccine; negotiations ended in March 2002 MVP decided to pursue development of a Men A conjugate vaccine using a different strategy: Creation of a partnership : Identify sources of raw materials (Men A PS and tetanus toxoid) Identify a conjugation method Find a vaccine manufacturer willing to accept technology transfer (fermentation and conjugation) and make the conjugate vaccine at a price less than $US 0.50 per dose 6

7 The Meningitis Vaccine Project (MVP) Preparation and characterization of a meningococcal conjugate vaccine PsA-TT Ps = mena polysaccharide conjugated to a protein carrier TT = tetanus toxoid Efficient, reproducible and scalable method to produce MenA conjugate Vaccine development according to international standards 7 Source: Lee CH, Kuo WC, Beri S, et al. Preparation and characterization of an immunogenic meningococcal group A conjugate vaccine for use in Africa. Vaccine 2009;27:

8 The Meningitis Vaccine Project (MVP) Development model Clinical grade Group A polysaccharide (PsA) produced by SynCo BioPartners, Amsterdam, Netherlands, for initial development, then transferred to Serum Institute of India (SIIL) Raw material (PsA) Lyophilization and stabilization tech transfer from Aerial, Illkirsch, France to SIIL Raw material (TT) Process development Manufacturing Core Team Conjugation method Conjugation method developed at CBER/FDA, Bethesda, USA, then transferred and scaled-up at SIIL Process development and manufacturing at SIIL Target price US$ 0.50/dose 8

9 Technology transfer from CBER to SIIL (1) Conjugation method December 2003 CBER Under the supervision of Dr Carl Frasch and Dr Robert Lee Two SIIL scientists at CBER for three weeks Conjugation method Process at lab scale SOPs for conjugation process and analytic methods 9

10 Technology transfer from CBER to SIIL (2) Technology transfer Production process and analytical methods transfered to SIIL team after a three-week intensive training at CBER (Bethesda), including the preparation of six lab-scale batches (10mg and 25mg of PsA) The technology of conjugation is well controlled by Indian scientists Subsequent implementation of the method at SIIL (Pune) 10

11 Technology transfer from CBER to SIIL (3) The Lee/Frasch conjugation method Structure of CBER/SII Men A Conjugate Vaccine January to March 2004: at SIIL Pune Implementation of the Lee/Frasch method Scale up to pilot scale (500 mg) Technical support from CBER scientists who visited SIIL (February 2004) Three lots of Men A conjugate sent from SIIL to NIBSC for testing (March 20, 2004) Murine immunologic studies done at NIBSC and SIIL Data presented at Expert Panel Meeting in June 2004 On going scientific support from experts: Dr C. Ceccarini, Dr J. Petre, Dr N. Ravenscroft 11

12 MVP & Partners Integrated Approach (1) Research/ Design Develop/ Validate Approve/ Recommend 1996 Epidemic meningitis, high priority in Africa 1999 Conjugate meningococcal vaccines needed 2001 Project Launch 2002 African political will for affordable vaccines, and Business model refined Tech transfer to SIIL 2005 Phase I trial Comprehensive vaccine development in India & Africa Enhanced disease surveillance Launch of carriage studies June 2010 WHO Prequalification (1-29 year-olds) following DCGI licensure Jan Regulatory approval at national level 2010 WHO/GACVS Recommendation & WHO/SAGE Policy 12 12

13 Men A conjugate vaccine - MenAfriVac sample 13

14 Why the tech transfers went well All parties committed to the goal of the project All activities covered contractually Mutual respect among all parties Communication, communication and more communication through periodic conference calls, annual review meetings Excellent technical staff Excellent document management Rapid decision-making process Strong support from the top and from the bottom 14

15 MVP & Partners Integrated Approach (2) Introduce/ Optimize Scale-up/ Apply Sept Phase1 introduction in 3 selected districts Dec Nationwide introduction in 3 countries Enhanced manufacturing capacity (SIIL) 2015 Introduction in routine EPI Mass campaigns 1-29 year-olds in 26 countries in Africa 2011 Burkina Faso initial measurement of vaccine impact 2012 Chad demonstration and quantification of the vaccine effect 2014 Impact evaluation framework defined 15 15

16 Vaccine effect on disease and carriage & transmission in Chad single dose mass vaccinations in 1-29 year-olds ( end of 2011) Source: Lancet

17 MenAfriVac rollout accross countries Target Countries: Burkina Faso, Mali, Niger, Nigeria, Chad, Cameroon, Sudan, Ghana, Benin, Senegal, Ethiopia, DRC, South Sudan, Cote d Ivoire, Togo, Uganda, Guinea, The Gambia, CAR, Eritrea, Kenya, Burundi, Guinea Bissau, Mauritania, Rwanda, Tanzania

18 18 MenAfriVac rollout ( N of doses )

19 MVP and MenAfrivac Well defined target product profile Successful approach for transfer of technology to produce an effective mena conjugate vaccine Compliance with international standards and prequalification requirements by WHO Sustained production of large volume at an affordable price Well planned and rapid introduction in countries of the meningitis belt Very high vaccination coverage 19

20 AARSH Recherche en Santé Humaine 20 In collaboration with health authorities of 26 countries in sub-saharan Africa and of India

21 21 Acknowledgement Dr Marie-Pierre Presiozi, director of MVP

22 Official launch day school children PATH/ Gabe Bienczycki 22