Approval Mechanism for Suppliers of Malaria Drugs and Nets Presentation by Dr Maryse Dugué RBM Partnership Secretariat, Malaria Medicines & Supplies Services Copenhagen – 310 January

Mechanisms 2 different mechanisms: Prequalification for drugs WHOPES testing of pesticides for public health

Pre-qualification of Drugs Manufacturers & Products Issues: a considerable number of sub- standard products and counterfeit anti- malarials Objectives: –To accelerate sustained access to, and use of, good quality ACTs –To ensure that adequate and effective treatment reaches significantly greater numbers of people in need –To assist/support the implementation of ACTs in ways that respond to the specific needs and requests of individual countries –To support drug regulatory agencies in regulating ACTs

Expression of Interest (EOI) - Artemisinin- based ACTs –Products selected: Artesunate (oral preparations, rectal prep.) Dihydroartemisinin (tablets, capsules, granules, suppositories) Artemether (oral preparations) Artemether/lumefantrine (oral preparations) Artesunate + amodiaquine (oral preparations) Artesunate + mefloquine (oral preparations) Artesunate (injection for IV and IM) Artemotil (injection forms) Artesunate + sulphadoxine/pyrimethamine (oral preparations) Pre-qualification of Drugs Manufacturers & Products

Multi-source combination antimalarial drug products - in majority of cases not typical “generic” drugs Usually generic drugs “well established” … –ACTs are relatively new, or very new drugs –Limited information available in public domain Most ACTs do not have quality standards For most ACTs reference standards not readily available –Reference standards available only for those that have pharmacopoeial monographs Difficulties of proving “interchangeability” Regulators have limited experience with this group of drugs...

Processes of Pre-qualification of manufacturers (of artemisinin-based combination antimalarial drug products) –Preparatory Phase Drafting of specifications and guidelines (products and product files) Publication of Expression of Interest (EOI) - IHT and WWW –Documentation Review Phase Receiving of EOI (letter+files) Screening, assessing, and reviewing dossiers  Report ……… Pre-qualification of Drugs Manufacturers & Products

Processes of Pre-qualification of manufacturers (of artemisinin-based combination antimalarial drug products) –Plant Inspection (GMP compliance) Phase Team of inspectors appointed by QSM/EDM Inspections carried out jointly with respective DRA –Reporting Phase Results in a “white” list of products and manufacturers. Pre-qualification of Drugs Manufacturers & Products

Assessment of dossiers –Carried out by teams of professionals from national DRAs (mix of developed and developing countries) Manufacturing sites inspections –Carried out by teams of three: WHO representative (qualified GMP inspector), inspector from well established inspectorate (PIC/S countries) and national inspector(s) Qualified inspectors pool limited, no additional capacities Pre-qualification of Drugs Manufacturers & Products

Issues with Prequalification of anti-malarials Status: so far only one combination prequalified: artemether/lumefantrine (Novartis) Several good candidates for artesunate+amodiaquine Need additional mechanism to make good quality formulations available to countries: joint tender WHO/UNICEF

Access to ACTs of Good Quality List of products/manufacturers evaluated as complying with GMP and other quality requirements Items included in the WHO WebBuy and UNICEF Supply Division catalogue List available on MMSS website:

Insecticides Treated Nets & quality assurance WHOPES collects, consolidates, evaluates and disseminates information on the use of pesticides for public health. Its recommendations facilitate the registration of pesticides by Member States. WHOPES is NOT a registration authority But: a product IS or IS NOT regarded as a LLIN after WHOPES evaluation PermaNet® 2.0 and Olyset Net® are currently the only LLINs recommended by WHO for malaria prevention and control

Quality control of nets Specifications have been developed only for polyester netting's and Olyset LLINs: resist more than 50 ISO normalized washes at 60°C Additional work on specifications ongoing (meeting in December 2005) Provisional QC procedure available

WHOPES testing/evaluation of long- lasting insecticidal mosquito nets PhaseType of StudyActivities Phase ILaboratoryRegeneration of insecticide and wash resistance Efficacy Phase IISmall-scale field trials Impact on vector behaviour Efficacy under different ecological settings Safety observations Phase IIIMedium- and/or large-scale field trials Long-lasting efficacy Community acceptance Safety observations

How to contact us… Malaria Medicines & Supply Services (MMSS) Roll Back Malaria Partnership Secretariat Website: Dr Maryse Dugué Manager Tel: +41 (0)