Quality of 2 nd line medicines for tuberculosis Ms Lisa Hedman World Health Organization Department of Essential Medicines and Health Products
Case studies in medicines for tuberculosis Outline: Statistics overview Quality standards: case studies of problems Access to quality medicines Challenges in generating clear demand for quality products
WHO REPORT 2011 GLOBAL TUBERCULOSIS CONTROL
Characteristics of market 650,000 of 9 million annual cases are predicted to need second line treatment will be children. Highest burden countries are low- and middle-income Manufacturing by international generics and local producers in highest burden countries Dx capacity is limited, inhibits demand for treatment Paediatric products are essentially unavailable
WHO Prequalified 2 nd line medicines Prequalification available: PQ suppliers Other SRA suppliers Amikacin, solution injection 500 mg/2 ml vial, amp; powder for injection 1g vial, amp 1 4 5 Capreomycin, powder for injection 1g, vial 0 1 1 Cycloserine, capsule 250 mg 2 1 3 Ethionamide, tablet /capsule 250 mg 2 1 3 Kanamycin, powder for injection 1g, vial 0 2 2 Kanamycin, powder for injection 500 mg, vial 0 2 2 Levofloxacin, tablet /capsule 250 mg, tablet 500 mg, tablet 750 mg 2 25 27 Moxifloxacin, tablet /capsule 400 mg 1 4 5 Ofloxacin, tablet /capsule 200 mg; 400 mg 2 20 22 Prothionamide, tablet /capsule 250 mg 0 0 0 Para-Aminosalicylic Acid (PAS) sachets, 4 g granules 1 0 1 PAS Sodium 100 g jar granules, 4g / 9.2 g sachets granules; powder for oral 0 0 0 Other SRA suppliers include sources identified in the US, Europe and Canada. Numbers are approximate and do not count potentially redudant sources. Total
Study of PQ and non PQ medicines Non-compliant Compliant 100% 80% 60% 45 43 32 15 41 67 2 12 40% 20% 17 9 6 1 0% Isoniazid tabl Isoniazid inj Rifampicin caps Kanamycin powder Isoniazid/Rifampicin tabl Ofloxacin tabl Ofloxacin caps Ofloxacin inf
No sample suspected to be of spurious, falsely-labelled, falsified or counterfeit product Failure rate Total = 11.3% 10.3% 1.0% 88.7% Compliant Nonextreme deviations Extreme deviations Extreme deviation arbitrarily defined as the content of API deviating by more than 20% from the declared content and/or average dissolution of tested units lower than 25% below pharmacopoeia Q value
Other cases studies Pakistan, May 2012: Toxic level of anti-malarial API replaced a standard excipient Over 120 deaths and 400 SAEs Green Light studies Patient outcome information was inconclusive Facilities reported mix of medicine sources and outcomes Literature searches did not yield studies on clinical outcomes Pharmacovigilance reporting not conclusive
Pharmacovigilance in TB medicines Country TB cases, 2010 report India 1,500,000 China 900,000 South Africa 400,000 Pakistan 270,000 Indonesia 239,871 Brazil 194,946 Bangladesh 160,000 Russian Federation 142,958 Philippines 93,261 Vietnam 87,848 3,988,884 x length of treatment x number of meds per patient Total pharmacovigilance needs
NEED ACCESS Other factors EML 2013 WHO PQ SRA Donors Pricing Policy Regulatory Financing Manufacturing Supply Demand (provider) Monitoring Stock outs
Policy and Prequalification Global policies and invitations for PQ are available but response and uptake to both are low.
Small market burdens of influence Example Countries Price controls Low price rules Mixed funders Exporter Production capacity China? WHO policies? India South Africa Financial influences availability Local policy
WHO REPORT 2011 GLOBAL TUBERCULOSIS CONTROL Some signals for national funding
Weak supply chain monitoring Consumption data? Prescription studies? Wastage figures? Where are the real data from countries?
Conclusion High risk environment Insufficient data to support "risk based" approach to quality assurance Available data show real problems