MDR-TB: Medicine quality and rational use

Transcription

1 MDR-TB: Medicine quality and rational use Hans V. Hogerzeil, MD, PhD, FRCP Edin Director, Essential Medicines and Pharmaceutical Policies WHO, Geneva 1

2 Can we rely on essential medicines against TB? (1) 2008: South-Africa Drug Regulatory Authority withdraws from the market two FDCs (Pyrazinamide-Ethambutol-INH-Rifampicin and INH-Rifampicin) produced in India. "Substandard tuberculosis medicines are particularly worth highlighting: there is little point in deciding optimum treatment regimens for TB when the medicines the patients actually use are not curative and/or encourage the spread of drug resistance" Paul Newton (BMJ : 427) 2

3 Can we rely on essential medicines against TB? (2) Quality defects found in: Botswana: 4/13 FDCs Nigeria: 4/4 INH, 3/3 Pyr, 5/15 Rif and 10/19 Strep inj India: Amikacin, Etham (2x), Rif (2x), INH (2x), Pyr Myanmar: Rifampicin Hong Kong, Pakistan, Germany: ofloxacin Rifampicin: Poor bioavailability in FDCs and monotherapy WHO study planned on the use and quality of TB medicines with NDRAs in Azerbaijan, Belarus, Kazakhstan, Ukraine, Uzbekistan 3

4 Direct reasons for WHO / UN prequalification Increased demand for affordable antiretrovirals (ARVs), anti-malaria combinations (ACTs), anti-tuberculosis drugs, diagnostics, and Reproductive Health (RH) commodities Large funds are available for public procurement (e.g. GDF, World Bank, UNFPA, Global Fund, PEPFAR, UNITAID) Increasing reliance on national procurement; increasing number of generic manufacturers offering products Little regulatory experience with new products, new combinations Challenges for UN family and national/global procurement agencies to ensure the supply of quality products 4

5 Prequalification basic principles Voluntary for participating manufacturers Legitimate - Procedures and standards approved through WHO Expert Committees, with Member States and Governing Bodies Widely discussed in technical fora - FIP congress 2002; ICDRA 2002, 2004 and 2006 (>100 national regulatory authorities) Transparent: all information on Open to innovators and multi-source/generic manufacturers No cost for applicants 5

6 Direct outcomes of prequalification List of products / manufacturers approved for UN procurement Meeting international norms and standards on quality, safety, and efficacy Better access to treatment More suppliers of good quality products, better supply security Fair competition based on assured quality, lower prices Harmonization of quality standards NDRAs, WHO disease programs, NGOs, procurement organizations Capacity building NDRA's: life-time learning experience in assessment and inspection Manufacturers: free feed-back on performance and advice how to improve 6

7 Not only one-time prequalification, but ongoing monitoring and requalification Fields samples taken after supply quality checks Routine inspections and ad-hoc inspections Changes and variations reported, assessed and recorded Products and manufacturers Requalification (re-assessment) after 5 years 7

8 Prequalification of priority medicines for MDR-TB: Status per 23 March 2009 Prequalified for UN procurement Cycloserine 250mg (1x) Ethambutol 400mg (2x) Ethionamide 250mg (1x) INH 100mg (1x), 300mg (1x) EIPR mg (4x) EI mg (1x) EIR mg (1x) IR mg (3x*), mg (1x), 30-60mg (1x) RIP mg (1x) New paediatric dosage forms! Pipeline: 36 products, including PAS granules, capreomycin 1g, levofloxacin 250mg, ofloxacin 200mg and prothionamide 250mg * One product listed but suspended with Notice of Concern 8

9 Wider context: Indirect benefits of prequalification Developing the necessary global quality standards Strengthening national regulatory capacity, speeding up regulatory uptake, promoting regional harmonization Strengthening quality control laboratories through capacity building and involvement in field testing Promoting generic production in developing countries Guiding innovation through clear specifications for FDCs and dosages and standards for quality and safety 9

10 Promotion rational medicine treatment of MDR-TB What is the problem? Only 62% of new and 5% of MDR- cases are treated in national TB programmes (NTPs) 48-96% are treated by private providers (China, India, Indonesia, Myanmar, Vietnam) without link to NTPs Low adherence to diagnostic and treatment guidelines; cure rate <50% in private sector 1 st and 2 nd line drugs widely available without prescription; leads to self-treatment, under-dosing, resistance If regulations exist, they are not well enforced 10

11 Proposed solutions to promote rational use: Mixture of managerial and regulatory approaches Managerial/financial approaches: Promote prescription and dispending by accredited facilities Prepare clear national treatment guidelines for public/private care Create financial incentives for prescribers (pay the provider properly) and for patients (free diagnosis and treatment; financial bonus?) Develop guidelines for health care providers (including pharmacies) to refer TB cases to accredited facilities Create financial bonus to refer patients (compensate income loss) Regulatory approaches: Stop sales of TB medicines without prescription Stop sales of TB medicines by dispensing doctors 11

12 Conclusion Reliable quality of medicines is absolutely essential for effective TB programmes (many examples of bad quality) WHO / UN prequalification programme Restrict procurement to prequalified medicines (GF quality policy) Monitor quality of TB medicines in NTPs and private sector Rational use improves treatment outcomes, promotes cost-effectiveness, prevents resistance and MDR-TB Clear clinical guidelines on diagnosis and treatment Promote free treatment in public sector and accredited facilities (give realistic financial incentives) Restrict free sales of medicines against TB and MDR-TB 12