Presentation on theme: "Quality Problems with Antimalarials"— Presentation transcript:
1 Quality Problems with Antimalarials Dr Mary R. CouperQuality Assurance and Safety: MedicinesWorld Health Organization
2 Quality of MedicinesGood quality medicines are essential to promote public health - in some African countries 30-50% of samples tested are of poor quality429 samples from Cameroon, Madagascar, Chad tested - 18% failed, 16 were counterfeit175 samples from Tanzania tested - 17% failed581 samples from Nigeria tested - 48% failed788 samples tested in Zimbabwe - 17% failed
3 Identifying quality problem Seven-country study: antimalarial quality differs among countries - content and dissolution problemsSamples were judged to have “failed” if content was <93% or >107%, and dissolution <80% in 45 minutes.Samples were judged to have “failed” if content was <90% or >110%, and dissolution <65% in 30 minutes.
4 Quality problemsMany African countries medicines are sold in open market places and by street vendorsMany medicines are smuggled or imported illegallyMost domestic manufacturers do not meet Good Manufacturing PracticesStorage and distribution conditions are inappropriateCorruption is a serious problem
5 About 50% of the countries in sub-Saharan Africa have very limited/no capacity to control the market-where regulatory authorities exist enforcement is weak
6 Antimalarial Drugs on WHO’s Essential Drug List artemether + lumefantrine (core)chloroquine (core)primaquine (core)quinine (core)doxycycline (comp.)sulfamethoxazole+pyrimethamine (comp.)artemether (restrict)artesunate (restrict)
7 Artemisinin derivatives available artesunate (oral)arteminol (dihydroartemisinin) (oral and rectal)artemether (oral and i.m.)artemether+lumefantrine (oral)artesunate (i.v. and i.m.)artemotil (i.v and i.m.)artesunate + mefloquine (oral)artesunate + amodiaquine (oral)artesunate + sulfadoxine/pyrimethamine (oral)
8 Quality concernsPartners in Roll Back Malaria, such as WHO, UNICEF, and UNDP, and many other UN organizations are involved in the procurement of antimalarial drugs.The supply of antimalarial products that are effective and of acceptable quality has become a major concern at both international and country level.
9 Prequalification scheme Why was the launch considered?Countries and other interested parties asking WHO to initiate pre-qualification of essential drugs referring to positive experience of vaccines pre-qualificationIncreasing pressures to increase access to artemisinin derivatives owing to resistance… but artemisinin combinations are not typical “generic” drugs
10 Not Typical “generic” drugs Usually generic drugs “well established” …Artemisinin combinations are relatively new, or very new drugsLimited information available in public domainFor most artemisinin products reference standards not readily available and for combinations no “originator” product existsDifficulties of proving “interchangeability”Regulators have limited experience with this group of drugs ...
11 Activities of Prequalification Scheme Assessment of dossiers: teams of professionals from national drug regulatory authorities:: Including Canada, Denmark, Estonia, Finland, France, Hungary, Indonesia, Malaysia, Philippines, Spain, South-Africa, Sweden and ZimbabweManufacturing site inspections: teamwork of inspectors: WHO representative (qualified GMP inspector), inspector from well-established inspectorate (Pharmaceutical Inspection Cooperation Scheme countries) and inspector(s) from national drug Regulatory authorities
12 Current Status 20 Product dossiers assessed 2 Manufacturers have been inspectedNo dossier meets WHO standards yetIncomplete data include lack of safety and efficacy data, lack of specifications for starting materials, information on method of manufacture of the product, lack of process validation, incomplete stability data.Assessment is ongoing
13 How WHO can help Issue guidelines and information Provide training seminars - 3 planned for 2003New monographs for all artemisinin based products recently published in International PharmacopoeiaProvide Basic Tests for confirmation of identity of active ingredient
14 Counterfeit40% of artemisinin-based antimalarials on the market are counterfeitNigeria reported 50% of the medicines on the market are counterfeitSome other African countries show that about 19% of products are counterfeit
15 Counterfeit database 2002Reports from 46 countries of which 3 are African countries:Zambia - chloroquine phosphateGabon - chloroquine and quinineTanzania - quinine