Approval Mechanism for Suppliers of Malaria Drugs and NetsPresentation by Dr Maryse DuguéRBM Partnership Secretariat, Malaria Medicines & Supplies Services

Copenhagen – 310 January 2006 10.2

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: http://rbm.who.int/mmss/procurement.html

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

Phase Type of Study Activities

Phase I Laboratory •Regeneration of insecticide and wash resistance•Efficacy

Phase II Small-scale field trials

•Impact on vector behaviour•Efficacy under different ecological settings•Safety observations

Phase III Medium- 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: http://rbm.who.int/mmss/

Dr Maryse Dugué

Manager

Tel: +41 (0)22 791 4439

E-mail: duguem@who.int