1. Quality Problems with Antimalarials
Dr Mary R. Couper
Quality Assurance and Safety: Medicines
World Health Organization

2. Quality of Medicines
Good quality medicines are essential to promote public health - in some African countries 30-50% of samples tested are of poor quality
429 samples from Cameroon, Madagascar, Chad tested - 18% failed, 16 were counterfeit
175 samples from Tanzania tested - 17% failed
581 samples from Nigeria tested - 48% failed
788 samples tested in Zimbabwe - 17% failed

3. Identifying quality problem
Seven-country study: antimalarial quality differs among countries - content and dissolution problems
Samples 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 problems
Many African countries medicines are sold in open market places and by street vendors
Many medicines are smuggled or imported illegally
Most domestic manufacturers do not meet Good Manufacturing Practices
Storage and distribution conditions are inappropriate
Corruption 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 concerns
Partners 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-qualification
Increasing 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 drugs
Limited information available in public domain
For most artemisinin products reference standards not readily available and for combinations no “originator” product exists
Difficulties 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 Zimbabwe
Manufacturing 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 inspected
No dossier meets WHO standards yet
Incomplete 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 2003
New monographs for all artemisinin based products recently published in International Pharmacopoeia
Provide Basic Tests for confirmation of identity of active ingredient

14. Counterfeit
40% of artemisinin-based antimalarials on the market are counterfeit
Nigeria reported 50% of the medicines on the market are counterfeit
Some other African countries show that about 19% of products are counterfeit

15. Counterfeit database 2002
Reports from 46 countries of which 3 are African countries:
Zambia - chloroquine phosphate
Gabon - chloroquine and quinine
Tanzania - quinine

16. Examples of Counterfeit

19. Challenge
Quality of products can only be achieved by building reliable and effective national regulatory authority