2. Access to anti-TB medicines WHO/EDM Technical briefing seminar for international staff active in pharmaceutical support programmes Salle G, WHO HQ 30 Sept - 4 Oct 2002 Dr S. Phanouvong Focal point for access to TB drugs EDM and STB Acknowledgements to Drs I. Smith and L. Blanc STB for the materials used in this presentation

3. Presentation outline  The Global targets in TB control  The constraints in DOTS expansion  The Global TB Drug Facility (GDF)  Operations  to date achievements  The Green Light Committee

4. DOTS case detection and cure  In 2002 Smear+ cases ave. cure rate of 80% in all DOTS programmes (70% in African region) 148 countries adopted DOTS strategy (incl. 22 high- burden ones which bear 80% of est. incidents cases) 55% of global pop had access to DOTS 27% of infectious cases were detected and treated under DOTS  TB remains as global health problems  2 billion of the world pop. is infected with TB bacillus 75% of cases in economically productive age group About 8.7 million develop active TB every year About 2 million deaths annually

6. Constraints in DOTS expansion  Some political/programmatic constraints Lack of or weak political will and commitment Lack of institutional/infra. to provide services inadequate supply of good quality TB drugs  shortages of 1 or 2 drugs  Emergence of MDR-TB  >3% of new cases 1996-1999  HIV-AIDS epidemic

7. Constraints in DOTS expansion (c.)  Operational and managerial TB treatment is seen as complicated&takes time  many tablets/capsules to be taken  too many drug formulations (different dosage strengths- esp. the FDCs)  requires DOT for potential success in treatment. DOT is not strictly applied in drug taking Lack of effective co-ordination in a decentralised system  for drug procurement, distribution and use

8. R- rifampicin, H- isoniazid, E- ethambutol, Z- pyrazinamide, T- thioacetazone 300150 40075150 300 75150 100 T 500150 1 [RHZ] int.3x w 275400751501 [RHZE] 50Compl. 2 [TH] 15030602 [RHZ] daily 60 2 [RH] int. 3x w 30603 [RH] 4001501 [HE] EZHR Combination (mg)No. formulations Essential anti-TB FDCs in WHO Model List

9. Need for Standardisation 19 TB products for 6 drugs on the WHO Model Essential Drugs List (and many other products in use by national programmes) 11 regimens approved by WHO in 3 treatment categories 2 recommended dosages - daily and intermittent 3 weight categories (not always consistent!) Variety of packaging: blisters, foil wrapped, loose tablets Confusion Inefficiency

10. “Securing access to high-quality TB drugs” Global TB Drug Facility

11. What is the GDF? A global initiative to secure access to high quality drugs to accelerate DOTS expansion, addressing four needs: –The need for more resources for TB drugs –The need for high quality TB drugs –The need for efficient procurement systems –The need for standardised products

12. GDF Operations Applications and Review –Continuous applications, with specific criteria and conditions –Independent Technical Review Committee (TRC) to assess applications Procurement –Procure and supply quality drugs via a transparent, competitive bidding process Monitoring –In-country and GDF operations

13. What does the GDF offer? Now –Grants of first line drugs, to support DOTS expansion –A direct procurement mechanism for countries and NGOs, for use in DOTS programmes –A web-based tool for placing orders and tracking shipments Future –A list of ‘prequalified’ manufacturers of quality TB medicines –Diagnostics and second line medicines

14. GDF Operations Application Eligibility criteria Specific conditions Standard form Supporting documents Supply Pooled procurement Standard products High quality Low cost Review Independent Committee 12-15 members meets 3x/year Country visit Monitoring Quarterly reports Existing monitoring Independent verification Results based

15. Applications & Review Eligibility for grants of first line drugs –Annual per capita GNP under $3,000 (low and lower middle income countries) –Priority for countries with a per capita GNP under $1,000 Documents needed to support application –National plan & budget for DOTS expansion to meet global targets –Technical guidelines demonstrating commitment to principles of DOTS –Annual report on DOTS performance (WHO TB database collection form) –Recent external review Review –Technical review committee of independent experts –Continuous application and review process, with TRC meetings at least 3 times a year –Emergency applications can be reviewed urgently –Support provided in principle for three years (renewable)

16. GDF Conditions Applicant has multi-year plan for DOTS expansion to reach global targets For treatment of TB patients, free of charge, in DOTS programmes using WHO approved treatment regimens Applicant responsible for payment or waiver of import duty or tax, storage fees or insurance levied on GDF drugs. Applicant responsible for in-country distribution of drugs Where registration of GDF drugs is required, applicant will facilitate this process Applicant agrees to independent monitoring of programme performance GDF support does not displacement already committed funds for DOTS Financing and technical assistance for other aspects of DOTS available

17. Country visits GDF team visit to countries approved or under consideration countries to: –Brief on GDF support and implications of grant –Assist countries to fulfil conditions, including development of plan, if necessary –Confirm fulfillment of conditions for GDF support –Confirm numbers of patients to treat, quantities and specifications of drugs required, preferred date of delivery –Overview of drug procurement and distribution system

18. Who are the donors of GDF? An initiative of the Global Partnership to Stop TB aiming to provide free drugs for 10 million people with TB by 2005 Needs $250 million over the next 5 years Initial funding from Canada, Netherlands & US

19. Monitoring Countries will receive drugs every year subject to: –Monitoring of performance by an independent technical agency –Compliance with GDF terms and conditions –Progress reviews and reports Reporting: Program, Financial, and Drug Management –receipt of drugs, custom clearance, registration –quarterly reports on case finding and treatment outcome –annual report on DOTS performance and financing –annual independent evaluation Monitoring report goes to TRC for decision on continuation of support

20. To date achievements Processed applications from 43 countries; 33 countries approved for support, and 1 pending Drugs ordered for 21 countries and delivered to 11 countries Drugs committed for almost 1,600,000 patients New funds received from donors (CIDA, US & Dutch) ~ $11m Drug prices down ~30% Average drug cost per patient: ~$11.2 Catalyst for introduction and expansion of DOTS Catalyst for standardisation - FDCs

21. GDF Cost per Regimen *All costs FOB, based on 40-55kg weight band, in US$

22. Assessment GDF monitoring Year 1Year 2Year 3 Country makes application Review by TRC Country visit First delivery Grant agreement Second delivery Third delivery Review by TRC Review by TRC Review by TRC Monitoring mission Monitoring mission Monitoring mission Desk audit

23. Countries Countries under consideration for GDF support Countries approved for regular GDF support Countries approved for emergency GDF support

24. Source: Rajesh Gupta et al. Responding to market failures in tuberculosis control. Policy Forum: Public Health. Science’s Compass, Science, vol. 293 10 Aug 2001. www.sciencemag.org Cost of MDR-TB treatment regimens

25. The Green Light Committee Members : Centers for Disease Control and Prevention, Harvard Medical School, Médecins Sans Frontières, National TB Programme - Peru, The Royal Netherlands Tuberculosis Association, and World Health Organization Established in WHO: March 2000 Major obstacle to implementing DOTS-Plus pilot projects is the high costs of SL anti-TB drugs

26. Examples of GLC drug prices  Capreomycin : monopoly,non-patent - Eli Lilly&Com. Open market unit price: $22.00 - $31.00 GLC unit price: $1.00 - $1.75 Reasons for price decrease: concessional price with Lilly, increased competition, expired patent, and pooled procurement  Cycloserine : monopoly, non-patent - Eli Lilly&Com. Open market unit price: $2.99 - $3.99 GLC unit price: $0.13 - $0.75  Ofloxacin : monopoly, patent - Aventis Open market unit price: $1.27 GLC unit price: $0.40 - $0.45

27. Contact the GDF http://www.who.int/gtb/policyrd/DOTSplus.htm Mailto:dotplus@who.ch mailto:gdf@who.int http://www.stoptb.org/GDF/default.asp Contact the MDR-TB/GLC