antimalarial medicines: current status in africa dr clive ondari medicines policy and standard...

Antimalarial Medicines: Current Status in Africa

Dr Clive Ondari

Medicines Policy and Standard DepartmentWHO/HQ

Department of Medicines Policy and Standards

2

Access framework

RationalSelection & Use

Reliablehealth and

supply systemsAffordable

prices

Sustainable

financing

ACCESS


3

Scope of the presentation

Situation analysis on antimalarials in Africa WHO recommendations on combination antimalarials (ACTs) Characteristics of ACTs (from a regulatory angle) Process of regulation of antimalarials Conclusions


4

Situation analysis: the challenges

Quality of antimalarial drugs has been declining.

The efficacy of (affordable) antimalarial drugs has been declining (drug resistance) and high cost of replacement options.

60-90% of the population seek initial treatment from non- public sector, i.e. street vendors, kiosks.

Supply of drugs is often inefficient and unreliable.


5

Failure rates (%) – Content (2003)

0

20

40

60

80

100

Gabon

Ghana M

ali

Kenya

Moz

ambiq

ue

Zimba

bwe

Sudan

Chloroquine Syrup

Chloroquine Tablets

Sulphadoxine/Pyrimethamine Tablets


6

0

20

40

60

80

100

Perc

en

t F

ail

ure

(%

)

Chloroquine Tablets SP Tablets

Failure Rates (%) – Dissolution (2003)


7

Malaria distribution and reported case of resistance or treatment failure


8

Factors leading to development of resistance

Lack of guidelines/poor drug treatment policies

Irrational prescribing

Irrational drug use

Drug concentration “tail” – poor formulations

Liberalized, uncontrolled drug market leading to poor quality products circulating in international and domestic markets


9

Artesunate + amodiaquine

• Artemether/lumefantrine

Artesunate + SP

Artesunate + mefloquine

FDC

ACTs

Amodiaquine + SP

Selection: Artemisinin-based Combination Therapies (ACTs)

MDT


10

Continent Countries Drug Line

AFRICA Burundi, Cameroon, Côte d'Ivoire, Democratic Republic of Congo, Gabon, Ghana, Guinea, Liberia, Madagascar, Mali, Senegal, Sao Tomé & Principe, Sierra Leone, Sudan (S), Zanzibar

AS + AQ 1st

Angola, Benin, Burkina Faso, Central African Republic, Comoros, Ethiopia, Gambia, Guinea Bissau, Kenya, Namibia, Niger, Nigeria, Rwanda, Uganda, S. Africa, Tanzania, Tchad, Togo, Zambia

AL 1st

Côte d'Ivoire, Gabon, Mozambique, Sudan (N), Sao Tomé & Principe, Zanzibar

AL 2nd

Mozambique, Sudan (N), South Africa (Mpumalanga) AS + SP 1st

ASIA Cambodia, Myanmar, Thailand AS + MQ 1st

Bangladesh, Bhutan, Laos, Saudi Arabia AL 1st

Indonesia AS + AQ 1st

Afghanistan, India (5 Provinces), Iran, Somalia, Tajikistan, Yemen AS + SP 1st

Viet Nam DP 1st

Papua New Guinea AS + SP 2nd

Philippines, Iran AL 2nd

SOUTHAMERICA

Ecuador, Peru AS + SP 1st

Bolivia, Peru, Venezuela AS + MQ 1st

Brazil, Guyana, Suriname AL 1st


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ACTs are not typical “generic” products

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 ...


12

WHO Pre-qualification of ACT Products 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

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


13

Cost implications of moving to ACTs

0

1

2

3

4

5

6

CQ SP AS/AQ AS/SP AT/LM AS/MF

Ave

rag

e co

st p

er a

du

lt t

reat

men

t (U

S$)

(2002)


14

Regulation of Medicines at National Level:

Drug Registration Manufacturing (enforcing GMP standards) Drug Distribution (scheduling: POM, PM, OTC/General Sales) Information and Promotion Control


15

Registration:

Safety Efficacy Quality Affordability (pricing)


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Who may apply for registration

Manufacturer Representative of a manufacturer (in the country of origin) –

power of attorney required An agent of a manufacturer (within the country) – power of

attorney required


17

Data required for approval of application

Chemical data (both active substance and formulating ingredients)

Pharmaceutical Data of the Product Complete formula of the product (including specifications) Manufacturing Processes (including validation data) Analytical and quality specifications of the finished product Method of analysis and assay of active ingredient in the

finished product Product stability profile

Clinical data (safety and efficacy)


18

Clinical Data

Innovator product s full documentation of preclinical and clinical safety and

efficacy according to ICH guidelines all claims on the SmPC have to be substantiated

Multi-source products Bio-equivalance demonistrated Direct evidence in support of safety and efficacy

SMPC = summary of product characteristics


19

Conclusions

In order to improve and sustain access to good quality, effective antimalarials in malaria-endemic countries, it will be necessary to intensify work to:

Develop and/or expand capacity for effective pharmaceutical regulation and control

Strengthen the capacity and efficiency of drug supply systems

Evolve more effective and efficient drug-financing arrangements

Ensure that antimalarial medicines are used in a rational manner

antimalarial medicines: current status in africa dr clive ondari medicines policy and standard...

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