1 |1 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 Access to Assured-Quality Praziquantel for the Control of Human Schistosomiasis Dr. Valerio Reggi - Department of Control of Neglected Tropical Diseases

2 |2 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 Global distribution of schistosomiasis From: Gryseels et al. Human schistosomiasis. Lancet 2006; 368: 1106–18 90% of infected people 76% of population at risk disease caused by worms of the genus Schistosoma

3 |3 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 Control of schistosomiasis is based on preventive chemotherapy interventions targeting the entire at-risk population

4 |4 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 Schistosomiasis - estimated infected population and population treated in 2008* Proportion treated/at-risk Proportion of total treated Received treatment Estimated at risk of infection, 2008 Estimated infected, 2008 WHO Region 2.01%66.86%11,700,000582,000,000214,000,000Africa 2.49%15.23%2,660,000106,600,00014,000,000Eastern Mediterranean <1%0.37%65,00051,000,0007,000,000Americas 14.71%17.54%3,060,00020,800,0001,300,000Western Pacific** 21.34%17.08%2,987,50014,000,000672,000China 2.29%100%17,485,000760,400,000236,300,000Global * As reported to WHO/NTD

5 |5 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 How much praziquantel is required/committed? Estimated need/commitment in million tablets Projected Need ? Donor funded~200 Merck KGaA Donation20 donor-funded demand in recent years: ~ 50 million tablets* Sudden demand increase: from 50 to >220 million tablets/year * B&M Gates Foundation/Schistosomiasis Control Initiative and Merck KGaA

6 |6 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 Praziquantel is made in large 600mg tablets Each 600mg Praziquantel tablet requires 640mg of API (assuming 94% yield) ~141 tonnes of API required for ~220 million tablets/year for the next 5-6 years

7 |7 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 Current manufacturers of assured-quality API and finished product may be unable to match demand increase Key concerns substandard quality RISKS interruption of supply scale-up failure higher prices Donor-driven demand and tight deadlines draw 'new' manufacturers into play

8 |8 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 QUALITY ASSURANCE POLICY FOR THE PROCUREMENT AND PROVISION OF PRAZIQUANTEL TABLETS* Proposed approach * adapted from Global Fund Quality Assurance Policy For Pharmaceutical Products - JOINT PLANNING OF NATIONAL REQUIREMENTS COORDINATED PROCUREMENT OF PZQ Current players: DFID, USAID/RTI, WHO

9 |9 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 QUALITY ASSURANCE POLICY FOR THE PROCUREMENT AND PROVISION OF PRAZIQUANTEL TABLETS FOR HUMAN SCHISTOSOMIASIS CONTROL (a) authorized for marketing by a stringent MRA; (b) listed as prequalified by the WHO Prequalification Programme; (c) positive opinion under Art. 58 of the EU Regulation 726/2004. Interim Measure establish an expert review panel similar to that established by the Global Fund

10 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 Expected advantages and benefits of PQ of PZQ API and finished products PQ of APIs would attract more generic manufacturers and increase competition PQ of APIs would enable local manufacture in large endemic countries Compared to stringent MRA's regulatory approval, PQ (both API and FP) can be faster and more flexible (e.g. no jurisdiction limitations, technical advice, capacity building) PZQ used in preventive chemotherapy of assured quality is reassuring for national authorities engaging in mass treatment campaigns Donor and national funding not wasted on poor-quality PZQ PQ capacity building component leads to more effective involvement of MRAs of endemic countries in development of new NTD medicines.

11 | Quality of Active Pharmaceutical Ingredients Beijing, 31 March 2010 Thank you