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REPUBLIC OF KENYA
MINISTRY OF HEALTH
Pharmacy & Poisons Board and Division of Malaria Control
Antimalarial Medicines in KenyaAvailability, Quality and Registration Status
A Baseline Study Undertaken Prior to Nationwide Distribution of Artemether-Lumefantine (AL) in Kenya
December 2007
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ACKNOWLEDGEMENTS ………………………………………………………….....4
Abbreviations and Acronyms………..……………………………………………………………..…...5.Foreword ………………………………………………………………………………………………..….6
Executive Summary …………………………………………………………………………………..…..7
1 INTRODUCTION AND BACKGROUND……………………………………....10
1.1 Malaria in Kenya…………………………………………………………………………….….10
1.2 Substandard and Counterfeit Medicines …………………………………………………..11
1.3 Drug Regulation in Kenya ……………………………………………………………….…...12
1.4 Study Justification ……………………………………………………………………….……13
1.5 Study Coordination and Technical Support……………………………………………..…14
1.6 Aim………………………………………………………………………………………………..14
1.7 Objectives ………………………………………………………………………………………14
2 METHODOLOGY …………………………………………………………….…15
2.1 Study Scope and Duration …………………………………………………………….……..15
2.2 Sampling ……………………………………………………………………………………......15 2.2.1 Facilities Surveyed ………………………………………………………………………….15 2.2.2 Medicines Surveyed …………………………………………………………………….… .16 2.2.3 Batch Sampling for Laboratory Testing ………………………………………………..…..16
2.3 Data Collection and Processing ……………………………………………………………..17 2.3.1 Data Collectors …………………………………………………………………………….....17 2.3.2 Data Collection ……………………………………………………………………………. …17 2.3.3 Data Verification and Analysis …………………………………………………………..…...17 2.3.4 Laboratory Analysis …………………………………………………………………………..18
3 RESULTS AND DISCUSSION …………………………………………….…...19
3.1 Availability of Antimalarial Medicines ……………………………………………………....19 3.1.1 Overall Range of Medicines …………………………………………………………….…..19 3.1.2 Range of Medicines in Provinces and Sectors ………………………………………….....19 3.1.2.1 Range of Medicines in Each Sector ………………………………………………......19 3.1.2.2 Range of Medicines in Each Province ……………………………………………......20 3.1.3 Range of Products Available ……………………………………………………………......21 3.1.3.1 Brands Available per Product ………………………………………………………....21 3.1.3.2 Products Available in all Sectors in all Provinces …………………………………....21 3.1.4 Origin of the Medicines ……………………………………………………………………...22 3.1.5 Artemisinin Combination- and Mono-therapy Medicines ………………………………...22 3.1.6 Availability of First-Line Treatment ………………………………………………………....23
3.2 Registration Status of Medicines …………………………………………………………....23
3.3 Quality Control ………………………………………………………………………………....24
TABLE OF CONTENTS
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3.3.1 Range of Samples Tested …………………………………………………………........….24 3.3.2 Quality Control Results ……………………………………………………………………..25 3.3.2.1 Results from National Quality Control Laboratory ……………………………….….25 3.3.2.2 Results from CENQAM ……………………………………………………………….26 3.3.2.3 Comparison of Results from NQCL and CENQAM ………………………………....26
3 SUMMARY OF RESULTS …………………………………………………....27
4 CONCLUSIONS ………………………………………………………………28
5 LESSONS LEARNT ………………………………………………………….29
6 RECOMMENDATIONS ………………………………………………………30
GLOSSARY …………………………………………………………………………...32
REFERENCES ………………………………………………………………………..33
ANNEXES ……………………………………………………………………………..35Annex 1: Data Collection Form ………………………………………………………………...35Annex 2: List of Pre-selected Medicines for Laboratory Analysis…………………………....36Annex 3: Drugs Analyzed at the National Quality Control Laboratory ……………………....37Annex 4: Drugs Analyzed at CENQAM ………………………………………………………..38Annex 5: Availability of Medicines in Each Sector …………………………………………....39Annex 6: Availability of Medicines in each Province ………………………………………... .40
ACKNOWLEDGEMENTS
This survey was undertaken through a collaborative project on access to essential medicines of the Ministry of Health, in collaboration with the World Health Organization and Health Action International-Africa, and with additional technical support from Management Sciences for Health (MSH). Financial support came from the UK Department for International Development (DfID) through the WHO Country Office - Kenya, and WHO facilitated the unique collaborative approach and coordinated the necessary technical support for the study. We duly acknowledge and appreciate the DfID funding and the technical support of all the partners; the National Quality Control Laboratory (NQCL) in Kenya and the Center for Quality Assurance of Medicines (CENQAM) in South Africa, where the samples were tested.
Special thanks are due to the following important contributors:
Advisory Group
Dr. Fred Moin Siyoi Chief Pharmacist, Ministry of Health; Registrar, Pharmacy and Poisons Board
Dr. Dorothy Memusi Division of Malaria Control, Ministry of Health
Dr. Steven Kimatu Head of Drug Information, Pharmacy and Poisons Board
Mr. George Muthuri Pharmacy and Poisons Board
Dr Abdinasir Amin Management Sciences for Health - Kenya
Ms Christa Cepuch Collaborations Manager, Health Action International – Africa
Dr. Regina Mbindyo National Professional Officer, Essential Drugs & Medicines Policy, WHO – Kenya
Ms Joanne Greenfield Malaria Advisor, WHO – Kenya
Dr. Augustine Ngindu National Professional Officer, Malaria, WHO – Kenya
Survey ConsultantProf Grace Thoithi Ag Dean, School of Pharmacy, University of Nairobi
Survey CoordinatorsDr. Jayesh Pandit Head of Pharmacovigilance, Pharmacy and Poisons BoardDr. Andrew Nyandingisi Pharmacist, Division of Malaria Control, Ministry of Health
Field Data CollectorsAli S. Kidzuga William Karema Omar Farah IbrahimAbdulahi M. Matan Ibrahim O. Mokaya Wilson Onduso
Peter N. Maina Andrew M. Kairu Grace K. Komen James K. Thuo Rose M. Kiunga Joseph M. Mutungi
Henry O. Lavisa Dr. Hadley Sultani Gideon K. Too Solomon K. Koech
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Abbreviations and Acronyms
ACT Artemisinin Combination TherapyAQ AmodiaquineAL Artemether-LumefantrineAM Antimalarial MedicineARV Anti Retro-Viral medicineASmP Artesunate-Sulphamethoxypyrazine-PyrimethamineB.P. British PharmacopoeiaCENQAM Center for Quality Assurance of MedicinesCQ ChloroquineDC Data CollectorDOMC Division of Malaria ControlHAI Health Action InternationalHPLC High Performance Liquid ChromatographyIM IntramuscularINN International Non-proprietary NameIPT Intermittent Preventive TherapyIV IntravenousKEMSA Kenya Medical Supplies AgencyMEDS Mission for Essential Drugs and SuppliesMOH Ministry of HealthNAT Non-Aqueous TitrationNQCL National Quality Control LaboratoryPh. Int. International PharmacopoeiaPPB Pharmacy and Poisons BoardWHO World Health OrganizationSP Sulphadoxine-PyrimethamineSmP Sulphamethoxypyrazine-PyrimethamineTB TuberculosisU.S.P. United States PharmacopoeiaUV Ultraviolet (spectrophotometry)
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Foreword
Access to quality, effective treatment is the cornerstone of any public health programme,
and it requires an effective regulatory system for medicines. Kenya's National Malaria
Strategy (2001-2010) identifies malaria control as a developmental issue, and highlights
drug regulation as an integral part of effective malaria case-management. The strategy
focuses on implementing interventions that are evidence-based, coordinated and totally
integrated, based on inclusive partnership between the MOH, other stakeholders and
development partners.
Kenya's malaria control efforts have recently begun to demonstrate positive results in
reducing morbidity and mortality. The use of effective drugs for malaria treatment, available
free of charge from public and mission health facilities, has contributed to this positive
result. This trend needs to be further supported by ensuring that only recommended
treatments for malaria are available and in use in Kenya, in line with global and national
treatment guidelines. The continued use of ineffective medicines undermines disease
control efforts, jeopardizes patients' health and wastes valuable resources. The medicines
regulatory authority plays a vital role of ensuring the quality, safety and efficacy of all
medicines in the market.
This anti-malarial survey, undertaken jointly by the Pharmacy & Poisons Board and the
Division of Malaria Control, is a bold step to create more direct linkages between medicines
regulation and treatment guidelines implementation. The findings should guide the PPB to
root out substandard anti-malarial medicines, and those that do not conform to regulatory
and treatment policy requirements. Further, the lessons learnt should guide an integrated
approach that addresses the wide range of pharmaceutical issues in disease control
interventions, including establishing regular medicines quality surveillance.
The multi-stakeholder approach of the study has drawn on technical expertise and
resources from government and partners, in line with the National Health Sector Strategic
Plan II and the sector-wide approach. Strategic areas for investment and support by
government and health sector partners are identified. It is anticipated that the collaborative
approach will continue in tackling the recommendations and the broader issues that the
study highlights.
Dr Fred Siyoi Dr Willis AkhwaleRegistrar, Pharmacy & Poisons Board Head, Division of Malaria Control
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Executive Summary
Background: To provide regulatory support to the malaria treatment policy in Kenya, a
baseline study of antimalarial medicines was undertaken in May 2006, immediately
following introduction of the new malaria treatment guidelines, and prior to nationwide
distribution and deployment of artemisinin combination therapies in the country. The
survey aimed to provide baseline information to guide implementation of the MOH malaria
treatment policy and to identify strategic issues for strengthening the national medicines
regulatory system. The results and recommendations would guide the MOH, health sector
development and implementing partners in making appropriate inputs and policy
interventions to ensure availability of safe, efficacious and quality medicines in the country.
Method: Data on availability of antimalarial medicines was collected from 200 facilities
nationwide, covering public, mission, private and general retail (informal) outlets, using a
survey methodology adapted from WHO and HAI. Registration status of the medicines
was verified by the Pharmacy and Poisons Board (PPB). Selected medicines were
sampled and their quality tested at the National Quality Control Laboratory (NQCL) and
some at the Center for Quality Assurance of Medicines (CENQAM), a WHO pre-qualified
laboratory.
Results
Availability: Forty unique formulations of antimalarial medicines were found in the market,
and of these, only 11 formulations (27.5%) are in the revised national malaria treatment
guidelines. A total of 187 antimalarial products were found, comprising innovator brands,
branded and non-branded generics. Sulphadoxine-pyrimethamine (SP) tablets had the
highest number of products (31); other commonly available medicines were amodiaquine,
artemether, artesunate, dihydroartemisinin and quinine. Artemether-lumefantrine (AL),
the first-line treatment for uncomplicated malaria and quinine, first-line treatment for
severe malaria were available in all the formal sectors in all provinces. Six oral artemisinin
mono-therapy formulations were found. The antimalarial medicines found in the country
were manufactured in 20 different countries by 113 manufacturers. Fourteen of these
manufacturers were from Kenya, and they accounted for 48.3% of the samples
encountered in the market.
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Registration Status: Of the products found in the market, 42.6% of them were registered
by the Pharmacy and Poisons Board, 42.2% were not registered and the registration status
of 15.2 % of the products could not be established. Of the unregistered products found in
the market, the majority were from Kenya and India.
Quality Control: Overall, 7 of the 43 batches tested at either of the two laboratories failed
analysis, a failure rate of 16%. The drugs that failed were amodiaquine tablets, quinine
mixture and tablets, artemether injection and sulphadoxine-pyrimethamine (SP) tablets.
Conclusions
1. A wide range of antimalarial medicines are available in the market, and the majority of
them are not in current national malaria treatment guidelines.
2. A high proportion of the antimalarial medicines were un-registered, with the majority of
un-registered products originating from Kenya and India.
3. Some medicines found in the market did not meet quality standards. Of particular
concern in relation to the guidelines, are SP, artemether injection and quinine tablets.
Key Lessons Learnt
1. Government leadership is crucial to systematically address medicines quality and
safety.
2. There are gaps and challenges in enforcing medicines regulation in Kenya. Capacity
building in this area is an ongoing process that requires coordinated partner support
3. Medicines regulation and disease control strategies are interdependent and require
a systematic and collaborative approach. Disease control programmes and the PPB
can work together, to positively influence and mutually support public health.
4. There is a lack of strategic engagement on medicines regulation at the wider health
sector level, and a lack of awareness of the role and work of the medicines regulator
(PPB).
5. The capacity of the WHO pre-qualified laboratory in South Africa is overstretched, and
there is need to enhance national capacity for medicines quality control.
6. Access to prompt and effective treatment is a pillar of the National Malaria Strategy, and
this cannot happen without an effective medicines regulatory authority. This applies to
all key public health programmes.
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Key Recommendations
1. PPB should enforce the withdrawal from the market of all non-recommended and
sub-standard malaria medicines, and enforce compliance with set pharmaceutical
regulations.
2. Computerize fully data management for medicines registration; information on
registration status of products should be readily accessible to the public.
3. Establish a post-market surveillance system to curb sub-standard and unregistered
products in the market.
4. Local QC laboratory capacity should be enhanced, including all necessary support
towards WHO pre-qualification.
5. Medicines regulation should link to the broader health sector planning and M&E, to
guide coordinated support to this important health sector function.
6. Consumers should participate actively in medicines regulatory issues, including
reporting of suspected sub-standard or counterfeit medicines to the PPB.
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1 INTRODUCTION AND BACKGROUND
1.1 Malaria in Kenya
Malaria is a leading cause of morbidity and mortality in Kenya, mostly affecting the rural
poor, especially young children and pregnant women. It accounts for 30% of outpatient
attendance and 19% of admissions to health facilities. Malaria is the most important cause
of death in children under 5 years of age and is estimated to cause 20% of all deaths in this
age group. In spite of this situation, malaria is a preventable and curable disease.
Evidence shows that malaria can almost always be successfully managed with positive
outcomes when safe and effective medicines are readily accessible to, and used rationally
by the population. Ensuring all of this is challenging, especially in countries experiencing
the trend of increasing resistance to many traditional first-line therapies. Kenya is no
exception, a country where resistance to chloroquine (CQ) is above 60%, to sulfadoxine-
pyrimethamine (SP) around 23% and to amodiaquine almost 8%.
The Ministry of Health (MOH) has prioritized malaria as one of the diseases for control and
has developed the National Malaria Strategy (2001-2010) and the National Health Sector
Strategic Plan II (2005-2010). The Strategy outlines interventions aimed at reducing the
morbidity and mortality associated with malaria. A key component is a change in the malaria
treatment guidelines, adopting Artemisin-based combination therapies (ACTs) as first-line
treatment for uncomplicated malaria. Artemether-lumefantrine (AL) is the ACT selected for
public procurement and distribution to government and mission facilities. To facilitate
implementation of the Strategy, the Division of Malaria Control (DOMC) developed detailed 1guidelines for malaria case management. These guidelines are summarized in Table 1.
Prior to these guidelines, artemether-lumefantrine (AL) had only been used in Kenya to a
small extent in the private and mission sectors, as it had not yet been made widely available
in the public and mission sectors, where the majority of Kenyans access treatment for
malaria. The MOH has only recently introduced this new medicine into the public and
mission sectors through financing from the Global Fund. The product is being procured
through a special arrangement between the manufacturer (Novartis), and World Health
Organization (WHO), providing it at cost to countries that have adopted AL as first-line
treatment for malaria. The product being procured for Kenya is pre-qualified by the WHO,
and is therefore expected to meet the minimum national standards of quality and efficacy.
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Introduction of this new treatment entails a fundamental change in the management of
malaria, and is expected to result in significant reduction in malaria morbidity and mortality
for all age groups, and particularly for children less than 5 years, the age group most
affected by malaria in Kenya.
Table 1: Treatment guidelines for malaria in Kenya (Summary)
IM: Intramuscular. IV: Intravenous.
1.2 Substandard and Counterfeit Medicines
According to the WHO definition the term 'substandard' is used to describe the quality
status of genuine drugs produced by legitimate manufacturers. A drug is considered
substandard, if, upon laboratory testing in accordance with the specifications it claims
to comply, it with fails to meet the specifications. A counterfeit medicine is defined by
WHO as “a medicine which is deliberately and fraudulently mislabeled with respect to
identity and/or source. Counterfeiting can apply to both branded and generic products
and counterfeit products may include products with the correct ingredients or with the
wrong ingredients, without active ingredients, with insufficient active ingredients or with 2fake packaging.”
Condition Medicine Strength FormulationUncomplicated malaria Artemether-Lumefantrine 20 mg/120 mg Tablets (Co-formulated, individual dose packs for specific weight categories)
Severe malaria Quinine dihydrochloride 600 mg/2ml Injection(IM/IV phase)
Severe malaria Quinine sulphate 200 mg or 300 mg Tablets(Continuation phase) or Quinine dihydrochloride 300 mgAll trimesters pregnancy or Quinine bisulphate 300 mgChildren below 5Kg or Quinine hydrochloride 300 mgIntermittent Preventive
Prophylaxis non-immune Mefloquine hydrochloride 250 mg Tabletsvisitors Atovaquone-Proguanil 250 mg/100 mg Tablets for adults
Atovaquone-Proguanil 62.5 mg/25 mg Tablets for children
Sulphadoxine- 500 mg/25 mg Tablets Therapy Pyrimethamine
Various studies and reports have been published on the quality and registration status
of medicines circulating in various world markets and the need to strengthen national
medicines regulatory systems, including post-market surveillance of quality and 3-9safety. In Kenya, quality studies done over the last three decades indicate failure
10-15rates vary with the type of medicine, the manufacturer and the country of origin. In
these studies, which involved analysis of hundreds of drugs over a period of years,
drug categories of greatest concern included antimalarials, antibiotics and anti-TB
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drugs, which consistently had failure rates of up to 30%. Electrolytes, skin preparations and vitamins/minerals all showed greater than 30% failure. Some individual drugs showed even higher failure than the category average. Amodiaquine and sulphadoxine-
16-18pyrimethamine (SP) have shown failure of up to 45% and 30%, respectively.
In Kenya, counterfeit drugs have been encountered in the market and some have been
detected during laboratory testing. These included antimalarials, antibiotics, antiretrovirals
and corticosteroid skin creams. The PPB has proceeded to take various measures,
including public alerts through media outlets, impounding the medicines and arresting the
perpetrators. Besides the studies on drug quality, there are other recent studies conducted 19-22in Kenya, to assess availability, cost and registration status of medicines. Findings have
indicated limited availability in some sectors, unregistered products in the market and
prices that are not affordable to the majority of the Kenyan population.
The majority of studies on quality of AMs in Kenya were undertaken by academia, and
focused mainly on the private sector and on a limited range of products. The studies
provided useful insights and made relevant recommendations on quality of products in the
market, but lacked linkages to regulatory follow-up and action on the findings. This is the
first study undertaken with the full participation of the regulator and MOH implementing
department, and covering the full range of products relevant to malaria control.
1.3 Drug Regulation in Kenya
The Pharmacy and Poisons Board is the drug regulatory authority of the Ministry of Health
Kenya, established in 1957 under the Pharmacy and Poisons Act, Chapter 244 of the laws
of Kenya. PPB has the mandate to regulate pharmaceutical services, ensure the quality,
safety and efficacy of human and veterinary medicines and medical devices, and advise
the Minister of Health on all aspects of medicines regulation, in order to safeguard the
health of Kenyans.
Within the PPB, the Department of Pharmacovigilance, set up in late 2004 is responsible for developing appropriate systems for detecting, reporting and monitoring adverse drug reactions within Kenya, as well as to develop and implement relevant tools and systems for post-market surveillance, to ensure that the quality and safety of medicines in Kenya meet the required standards. The scope of work for this department also encompasses other relevant issues such as medication errors, efficacy reporting, the use of medicines for indications that are not approved and for which there is inadequate scientific basis, case
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reports of acute and chronic poisoning, assessment of drug-related mortality, abuse and misuse of medicines, as well as adverse interactions of medicines with chemicals, other medicines and food. To achieve its objectives, the department links closely with the departments of medicines registration, pharmaceutical inspection, drug information and the National Quality Control Laboratory.
The National Quality Control Laboratory (NQCL) is the technical arm of the PPB
responsible for evaluating the quality of medicines and selected medical devices. The
NQCL carries out examination and testing of drugs and medical devices by use of
chemical, physical, pharmacological and other pharmaceutical evaluation. At the request
of the Board and on behalf of the Government, it tests locally manufactured and imported
drugs or medicinal substances with a view to determining whether such drugs or medicinal
substances comply with set standards. Whenever necessary, PPB utilizes the services of
a WHO-prequalified laboratory for analysis.
The NQCL is in the process of pursuing WHO pre-qualification, to enhance its capacity to
serve national and regional needs for medicines quality control.
1.4 Study Justification
Currently, therapeutic alternatives to artemisinin combination therapy (ACT) are limited
and thus it is crucial to safeguard the effectiveness of these medicines as much as
possible, through evaluating their safety and quality and ensuring their appropriate use.
To contribute to the overall evaluation and impact assessment of the new malaria
treatment guidelines, there was need to establish baseline information on the availability,
registration status and quality of the full range of antimalarial medicines (AMs) currently
being used in Kenya. This was a comprehensive baseline survey that covered all the major
health sectors and all geographical regions, rather than previous studies that covered
mostly the private retail sector and only selected districts or provinces.
The study was designed to provide a strategic linkage between national malaria control
and medicines regulation, and the findings will inform policy interventions to ensure that
the right AMs are in use in Kenya, and that they meet prescribed standards of quality and
safety. The lessons learnt will also strengthen the national medicines regulatory authority,
and ensure better alignment and responsiveness to disease control strategies.
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1.5 Study Coordination and Technical Support
The PPB undertook the survey, in collaboration with the Ministry of Health DOMC.
Technical support was provided by WHO and Health Action International (HAI)-Africa, in athe context of a global WHO/HAI joint collaborative project on access to medicines.
Funding for the study came from DFID (UK) through the WHO Country Office, and
additional technical support came from Management Sciences for Health (MSH). The PPB
established a 'Survey Advisory Group' comprising technical staff from the collaborating
departments and partners. This multi-stakeholder approach aimed to elucidate lessons for
the PPB in establishing comprehensive systems for the surveillance of medicines quality
and safety; and for DOMC towards better regulation of antimalarial medicines for the
success of the malaria control strategy. The survey also serves as a platform for the
engagement of other stakeholders interested in strengthening medicines regulation to
support disease control.
1.6 Aim
The aim of this survey was to establish baseline data on the current availability, registration
status and quality of antimalarial medicines in the public, mission and private health
sectors, as well as in the informal (general retail) sector in Kenya, prior to the introduction of
the new malaria treatment guidelines.
1.7 Objectives
The specific objectives of the survey were to:
1. Assess the range and availability of products for the treatment of malaria in the
three formal health sectors in Kenya (public, private and mission) as well as in the
general retail (informal) sector.
2. Determine the registration status in Kenya of each available antimalarial product.
3. Assess the quality of the available products through laboratory testing of a
representative sample.
4. Make appropriate recommendations, based on the findings, for improving
availability, quality and use of antimalarial medicines in Kenya.
a The goal of the WHO/HAI Collaborative Project is improved policies and practices to increase access to essential medicines
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2 METHODOLOGY
2.1 Study Scope and Duration
The study covered all antimalarial medicines in the market in all eight provinces in Kenya,
and data was collected from four defined sector outlets, namely public, mission, private
and general retail (informal) outlets. Public facilities were pharmacies in MOH provincial,
district or sub-district hospitals. Mission sector outlets were pharmacies in mission
hospitals and medicine outlets that are run by faith-based organizations. Private facilities
were privately-owned pharmaceutical retail outlets (chemists), while the general retail
facilities (informal sector) were supermarkets and small shops ('kiosks'). The field survey
was conducted in May 2006, and laboratory testing took place between December 2006
and September 2007.
2.2 Sampling
There were 3 aspects of sampling for this study, namely sampling of facilities and
medicines to be surveyed, and sampling of medicine products and specific batches for
laboratory testing.
2.2.1 Facilities Surveyed
The survey adopted a methodology developed by WHO and HAI, for measuring medicines 21availability and prices . A total of 192 facilities were sampled nationally, comprising six
facilities per sector in each of the eight provinces, thus totaling 48 facilities per sector or 24
facilities per province. For each province, the public provincial hospital was selected, as
well as five public district or sub-district hospitals. For each of these six public health
facilities, and within a 5-kilometer radius of the facility, one mission health facility, one
private health facility and one general store were selected. However, the actual number of
facilities visited was 200, due to situations encountered in the field, which led to fewer
facilities surveyed in three provinces; and more than 24 facilities visited in four provinces.
Table 2 gives the number of facilities visited for each sector in each province.
Table 2: Number of facilities surveyed in per sector per province
Province General Mission Private Public TotalCentral 6 7 8 7 28Coast 6 3 4 5 18Eastern 7 7 12 6 32Nairobi 7 7 7 7 28North Eastern 6 5 6 6 23Nyanza 4 4 6 6 20Rift Valley 6 6 7 8 27Western 6 6 6 6 24Total 48 45 56 51 200
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2.2.2 Medicines Surveyed
All antimalarial medicines found in the selected facilities on the day of data collection were
surveyed. Data was collected at each health facility using a standardized data collection
tool (Annex 1). The tool contained listed AMs presumed to be in the market (32
formulations), and allowed for any additional products to be included. A total of 40 unique
formulations were found in the market, and these were all included in the survey. Physical
samples were only obtained for a pre-selected list of eight (8) medicine formulations to be
subjected to laboratory analysis (see section 2.2.3).
2.2.3 Medicines for Laboratory Analysis
Whereas the data collection form captured relevant details for all antimalarial medicines
found in the facility, physical samples were not required for each medicine. Physical
samples for laboratory analysis were only obtained for eight (8) medicines (Annex 2), pre-
selected by the Survey Advisory Group on the basis of their relevance to the country's
previous and new malaria treatment policy. For the eight medicines, samples were
obtained for all batches of each product found in the facilities, and the samples collected
were sent to PPB, to be processed centrally for laboratory testing.
2.2.4 Batch Sampling for Laboratory Testing
Sampling of batches for quality control testing was done centrally at the PPB after all the
samples were received from the field, appropriately recorded and coded. This centralized
sampling was intended to minimize bias by blinding the data collectors as to which
products and batches would be sent to the laboratory for testing. Where similar batches
were collected from two or more facilities, the quantities were combined into one sample for
purposes of batch sampling. For each of the 8 medicine formulations collected from the
field, a representative number of batches for quality control testing were sampled as
follows:
Testing at NQCL: For each type of product, all batches collected were listed. Where more
than 3 batches had been collected, a random sample of N+1 batches was selected.
Where less than 3 batches of a product had been collected, all the batches were included
on the NQCL List. Batches that did not have sufficient quantities for testing were excluded
from the list. A total of 41 batches were thus sampled for testing at NQCL.
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Testing at CENQAM: The batch numbers randomly selected for analysis at the NQCL were
listed. From this list, a random sample of 14 (about 30%) of these batches was selected for
confirmatory testing at Center for Quality Assurance of Medicines (CENQAM), a WHO pre-
qualified laboratory in South Africa.
2.3 Data Collection and Processing
2.3.1 Data Collectors
There were sixteen (16) data collectors for the survey, comprising pharmaceutical personnel
from the public sector, drawn from health facilities located in or around the study areas. A
survey manager was engaged to coordinate the survey, assisted by two survey coordinators
from the PPB and the DOMC respectively. Most of the data collectors were experienced in
data collection on pharmaceutical products, and were already participating in an ongoing
MOH monitoring of medicines availability and prices. A two-day pre-survey training was
carried out in Nairobi to orientate the DCs on the rationale and methodology of the survey
and to pre-test and adapt the data collection tools. The Chief Pharmacist MOH issued each
data collector with a letter of introduction to facilitate the collection of data from facilities.
2.3.2 Data Collection
At each facility and for each anti-malarial product found in that facility, the following details
were recorded on the data collection form: name of facility and contact details; international
non-proprietary name (INN) and brand name of product, formulation, strength, pack size,
batch number, name of manufacturer, and country of origin.
Where a physical sample was required, this was obtained either free of charge or purchased
from the facility. Samples collected each day were coded and labeled appropriately by the
data collectors (DCs), and sent to the Pharmacy and Poisons Board by overnight courier.
Every attempt was made to ensure that the samples were appropriately handled during
collection, storage and transportation.
2.3.3 Data Verification and Analysis
The data collection forms and medicine samples were received at the PPB, verified for
completeness and accuracy and appropriately coded. Doubtful entries on the forms were
validated by contacting the data collector, the health facility or both. For the remaining data
collection tools, random verifications on the information collected were done by phone. The
medicine samples were sorted according to presentation and batch number, recorded and
kept in a secure store within the PPB premises.
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® ®Data from the tools was analyzed using Microsoft Access and Microsoft Excel . All data
entries were counterchecked against the tools and samples. The PPB Medicines
Registration Department verified registration status of the complete list of products found in
the facilities surveyed, using computerized drug registration records and in some cases,
manual checking of actual registration dossiers. Registration data was analyzed using an ® 21Excel workbook adapted from the WHO/HAI price survey manual.
2.3.4 Laboratory Analysis
All tablets were subjected to the tests of uniformity of weight, dissolution and assay. Oral
drops and mixtures were tested for microbial load and content of active pharmaceutical
ingredient (assay), while parenteral injections were tested for sterility and content.
Wherever possible, methods from official compendia, British Pharmacopoeia (B.P.),
International Pharmacopoeia (Ph. Int.) and United States Pharmacopoeia (U.S.P.) were
used. In cases where no compendia methods were available, the manufacturer's in-house
method was used as is or after adaptation. Annexes 3 and 4 give summaries of the tests,
methods and the compendia used for the drugs that were analyzed at the NQCL and
CENQAM, respectively. Each laboratory issued a certificate of analysis for the samples
tested, and NQCL prepared a separate detailed report of the actual method used to test
each sample and the result obtained.
19
3 RESULTS AND DISCUSSION
3.1 Availability of Antimalarial Medicines
3.1.1 Overall Range of Medicines
Thirty two formulations were presumed to be in the market (Annex 1), but a total of 40
different types of AM formulations were found (Annexes 5 and 6). Only 11 of the
formulations are in accordance with the revised national malaria treatment guidelines. The
40 formulations comprised 31 oral preparations (12 paediatric and 19 adult), 6 injectable
preparations and 3 suppositories.
All the medicines recommended in the treatment guidelines were encountered, except
atovaquone-proguanil, which was not found in any of the facilities. Of the medicines found,
amodiaquine, artemether, artesunate, chlorproguanil-dapsone, chloroquine,
dihydroartemisinin, dihydroartemisinin-piperaquine, halofantrine, primaquine and
proguanil are not recommended in the treatment guidelines. The most commonly available
medicines were sulphadoxine-pyrimethamine (suspension and tablets), amodiaquine
(suspension and tablets), artemether (tablets and injection), artesunate tablets,
dihydroartemisinin tablets and quinine (all dosage forms).
In each of the facilities, every antimalarial formulation that was found on the day of the
survey was given a sample number. Thus, there were 2535 samples found in the 200
facilities.
3.1.2 Range of Medicines in Provinces and Sectors
3.1.2.1 Range of Medicines in Each Sector
The private sector had the highest range of medicines and only primaquine tablets and
artemether suppositories were not found in this sector (Annex 5 and Table 3). Mission
hospitals had 30 (75%), while public hospitals had 27 (67.5%) of the full range of medicine
formulations. The general (informal) sector had 5 (12.5%) of the formulations, namely
amodiaquine (suspension and tablets), SP (suspension and tablets) and
sulphamethoxypyrazine-pyrimethamine tablets. The recommended first-line medicines,
i.e. AL tablets and quinine (tablets and injection) were found in all the formal sectors
(mission, private and public). AL suspension (not in the guidelines) was only found in the
private sector, and in only two facilities in (Annex 5).
20
In relation to the total number of samples encountered, the private sector had more than
half of the samples (59.2%), while the general (informal) sector accounted for 4.4% of the
samples. The number of samples from the mission and public sector are almost the same,
i.e. 20% and 16.4% respectively (Table 3).
3.1.2.2 Range of Medicines in Each Province
The number of medicines available in the provinces ranged from 24 for Coast to 34 for
Central province (Annex 6, Table 4). The number of facilities sampled in Coast, North
Eastern and Western provinces were relatively few (Table 2) and this is reflected in the
percentage of samples from these provinces. Although only 20 facilities were visited in
Nyanza, the results show that the province had a wide range of medicines and samples.
The wide range of medicines, most of which are not in the guidelines, may be an indication
of widespread lack of adherence to national treatment guidelines. For example,
chloroquine, to which there is a high resistance rate, was found in all provinces except
Coast province. On the other hand, the recommended artemether-lumefantrine tablets
and quinine (tablets and injection) were found in all the provinces.
Table 3: Proportion of medicines encountered in each sector
General Mission Private PublicNumber and % of medicine formulations(out of 40) Number and % of 112 (4.4%) 507 (20%) 1501 (59.2%) 416 (16.4%)samples encountered (out of 2535)
5 (12.5%) 30 (75%) 38 (95%) 27 (67.5%)
* Percentages do not add up to 100 since similar medicines were encountered in the different sectors
Central Coast Eastern Nairobi North Nyanza Rift Western Eastern Valley No and % of Medicine (85%) (60%) (82.5%) (82.5%) (70%) (72.5%) (72.5%) (67.5%)formulations(out of 40)No. and % of 15.9 7.5 18.6 11.9 6.9 11.4 18.2 9.6samples encountered(out of 2535)
34 24 33 33 28 29 29 27
Table 4: Proportion of medicines available in each province
21
3.1.3 Range of Products Available
3.1.3.1 Brands Available per Product
A total of 187 antimalarial products were found, with the number of pharmaceutical
products per medicine formulation ranging from 1 to 31. The products found comprised
innovator brands, branded generics (the majority) and unbranded generics. Table 5 shows
that SP tablets had the greatest number of products and were also the most widely
encountered (13.4% samples). Amodiaquine (tablets and suspension), artemether
injection, doxycyline and sulphadoxine-pyrimethamine suspension had many products
and were widely distributed. Artesunate and artemether tablets had few samples
encountered, but many products.
3.1.3.2 Products Available in all Sectors in all Provinces
The private sector had the highest number of products, followed by the mission and public
sectors. The general sector had the smallest number of products, and this is expected
since the range of medicines accessed through this sector are few. In this sector, high
numbers of brands were encountered in Nyanza and Eastern provinces. None of the
general facilities surveyed in the North Eastern province had any antimalarial medicines.
Generally, many products were encountered in the Rift Valley, Eastern and Central
provinces (Table 6).
Table 5: The most commonly encountered medicines
Medicine No. and % of products (N=187) (N=2535)Sulphadoxine-pyrimethamine tablets 31 (16.6%) 341 (13.4%)Amodiaquine tablets 18 (9.6%) 300 (11.8%)Amodiaquine suspension 16 (8.6%) 241 (9.5%)Artemether injection 16 (8.6%) 147 (5.8%)Doxycycline tablets/capsules 20 (10.7%) 142 (5.6%)Sulphadoxine-pyrimethamine suspension 18 (9.6%) 137 (5.4%)Artesunate tablets/capsules 23 (12.3%) 84 (3.3%)Artemether tablets 16 (8.6%) 79 (3.1%)
No. and % of samples
Table 6: Number of products found in each sector in each province
General Mission Private PublicCentral 6 46 110 31Coast 3 25 49 28Eastern 17 45 119 20Nairobi 3 53 67 34North Eastern - 23 59 16Nyanza 26 35 86 31Rift Valley 8 35 132 50Western 5 33 74 20
22
3.1.4 Origin of the Medicines
The products found in the market came from 113 different manufacturers in 20 countries of
Africa, Asia, Europe and North America (Table 7). Kenya, India and China were the most
significant countries in terms of origin of products found. Locally manufactured AMs were
the most frequently encountered (48.3% of samples), although they accounted for only 16
(14.2%) of the manufacturers. AMs from India accounted for the highest number of
manufacturers (33.6%), but only 16.5% of the samples encountered. AMs from China
accounted for the same number of manufacturers as Kenya (16), but only 9.1% of the
samples encountered. Countries in Europe accounted for few manufacturers each, but in
total, Europe accounted for 28.3% of the manufacturers and 19.7% of the samples. The
only medicines from the U.S.A. were two brands of doxycycline found in two mission
hospitals. These drugs were not registered and they may have entered the market as
donations. Three products from China and one each from Morocco, Senegal and South
Africa were manufactured for multinational companies based in Europe.
Table 7: Number of countries and manufacturers of medicines
Continent Country Manufacturers Percentage of SamplesAsia China 16 9.1
Hong Kong 2 aIndia 38 16.4Pakistan 2 2.0
Africa Kenya 16 48.3Morocco 2 aSenegal 1 3.3South Africa 1 aTanzania 1 a
Europe Austria 2 1.5Belgium 3 5.4France 6 2.9Germany 6 1.5Greece 1 aItaly 1 1.1Netherlands 4 aNorway 1 aSwitzerland 3 5.6UK 5 1.2
America USA 2 aa: Samples less than 1%
3.1.5 Artemisinin Combination- and Mono-therapy Medicines
Of the 12 artemisinin based oral medicines, six were combinations, namely AL (tablets
and suspension), artesunate-amodiaquine, artesunate-sulphamethoxypyrazine-
pyrimethamine, artesunate-mefloquine and dihydroartemisinin-piperaquine tablets
(Annexes 5 and 6). Although oral artemisinin based medicines should be used in
23
3.1.6 Availability of First-line Treatment
The recommended first line treatment for uncomplicated malaria, AL (tablets) was found in
all sectors and in all provinces (Annexes 5 and 6), but in only 33% of the facilities. (At the sttime of this survey, the deployment of AL as 1 line treatment was just starting, without a full
country-wide scale-up. (After the study, and following countrywide distribution of AL
through public and mission sector free of charge, availability of AL in these sectors has risen 6to over 90% and 80% respectively ). All formulations of quinine, the first-line treatment for
severe malaria, were widely available in all formal sectors and provinces.
3.2 Registration Status of Medicines
Out of all the products found in the market, 42.6% were registered by the PPB, 42.2%
were not registered and the registration status of 15.2% of the products could not be
established at the time of the survey. Medicines which had all their products registered
were AL tablets (5 products), artesunate-sulphamethoxypyrazine-pyrimethamine (1),
chlorproguanil-dapsone (1), dihydroartemisinin tablets (6) and halofantrine suspension
and tablets (2 each). Medicines which had many products in the market also had a high
proportion of the same not registered (Table 8) Of major concern are amodiaquin tablets
and suspension, artemether tablets and injection, artesunate tablets and capsules and
SP tablets and suspension, all of which were widely available (Table 8) in most sectors
and provinces (Annex 5 and 6).
.
b The availability and prices of selected medicines is monitored quarterly by MOH Division of Pharmacy, with technical support from WHO and HAI-Africa. Figures quoted are for the monitoring report of October 2007, which can be viewed at www.health.go.ke.
Table 8: Number of products registered for some of the most available drugs
Medicine Registered Not registered Not established TotalAmodiaquine 50 ml/5ml 7 9 0 16Amodiaquine tablet 200 mg 9 9 0 18Artemether tablets 9 5 2 16Artemether injection 5 7 4 16Artesunate tablets/capsules 10 11 2 23Doxycycline tablets/capsules 4 7 9 20Sulphadoxine/Pyrimethamine susp 7 11 0 18Sulphadoxine/Pyrimethamine tablets 15 13 3 31
combination with other antimalarial medicines, six mono-therapy formulations were found and these were artemether, artesunate and dihydroartemisinin suspensions and tablets. It is noteworthy that the PPB has since discontinued registration of AM mono-therapies, and has given notice to manufacturers and importers to stop producing or importing these monotherapies, and to re-register their AM products in accordance with national malaria treatment guidelines.
24
c All CENQAM samples had the same batch numbers as NQCL samples, except for two of the four SP samples, which were from the same manufacturer, but of different batch numbers.
Table 9: Products Analyzed in Quality Control Laboratories
Medicine NQCL CENQAMAmodiaquine hydrochloride 50 mg/5ml suspension 3 -Amodiaquine hydrochloride 200 mg tablet 9 -Artemether 80 mg/ml injection 2 -Artemether 100mg/ml injection 1 -Artemether 20 mg/Lumefantrine 120 mg tablets 1 1Artemether 180 mg/Lumefantrine 1080 mg/60 ml suspension 1 1Artesunate 50 mg tablets 3 -Dihydroartemisin 60 mg tablets 3 3Halofantrine 250 mg tablets 1 -Quinine dihydrochloride 200 mg/ml drops 2 1Quinine dihydrochloride 50 mg/ml mixture 2 1Quinine dihydrochloride 600 mg/2 ml injection 2 1Quinine bisulphate 50 mg/5 ml suspension - 1Quinine sulphate 200 mg tablets 1 -Quinine sulphate 300 mg tablets 2 -Sulphadoxine 500 mg/Pyrimethamine 25 mg tablets 6 4Sulphamethoxypyrazine 500mg/Pyrimethamine 25mg tablets 2 1Total 41 14
Table 10: Countries of origin for batches analyzed
Continent Country NQCL Samples CENQAM Samples
Africa Kenya 23 9Senegal 1 0South Africa 1 0
Asia China 3 2
India 7 0Pakistan 1 1
Europe Austria 1 0Belgium 2 0France 1 0
Greece 1 0Netherlands 0 1Switzerland 0 1
Total 41 14
3.3 Quality Control
3.3.1 Range of Samples Tested
Forty one samples were tested at the NQCL, and 14 samples at CENQAM, as
summarized in Table 9. A total of 43 unique batches were tested. This is because all
except 2 samples tested at CENQAM were the same batch as the samples tested at
NQCL. The 43 batches originated from 33 manufacturers based in 12 countries in
Africa, Europe and Asia (Table 10). Local manufacturers accounted for 23 (53%) of
the batches tested.
25
3.3.2 Quality Control Results
3.3.2.1 Results from National Quality Control Laboratory
The range of laboratory tests performed included weight uniformity, dissolution and assay
for tablets; microbial load and assay for oral liquids; and sterility and assay for injections
(Annexes 3 and 4). Of the 41 samples tested at NQCL, 36 samples (87.8%) passed and 5
samples (12.2%) failed to comply with quality specifications. The results of laboratory
testing at NQCL are summarized in Table 11 below.
Of the five samples that failed testing at NQCL, 3 failed on content of active ingredient and 2
failed the dissolution test. Four of the failed products were locally manufactured, while one
(artemether injection) was from India. Two of them (quinine mixture and SP tablets) were
from the same manufacturer. Out of the five samples that failed analysis, one was
registered, two were not and the registration status of two could not be established.
Two out of the nine samples of quinine analyzed (tablets and syrup) failed on the content of
active ingredient. This is of great concern because quinine is the first-line treatment for
severe malaria and could easily lead to treatment failure and resistance.
Table 11: Quality control results from NQCL
Medicine Samples tested failed failed (for failed
batches) Amodiaquine hydrochloride 50mg/5ml suspension 3 - -Amodiaquine hydrochloride 200mg tablet 9 1 Dissolution Not registeredArtemether 80mg/ml injection 2 1 Content Registered -Artemether 100mg/ml injection 1 - -Artemether 20 mg/Lumefantrine 120 mg tablets 1 - -Artemether 180mg/Lumefantrine 1080mg/60ml suspension 1 - -Artesunate 50mg tablets 3 - -Dihydroartemisin 60mg tablets 3 - -Halofantrine 250mg tablets 1 - -Quinine dihydrochloride 200mg/ml drops 2 - -Quinine dihydrochloride 50mg/5ml mixture 1 - -Quinine dihydrochloride 600mg/2ml injection 2 - -Quinine bisulphate 50mg/5ml mixture 1 1 Content Not establishedQuinine sulphate 200 mg tablets 1 1 Content Not establishedQuinine sulphate 300 mg tablets 2 - -Sulphadoxine 500 mg/Pyrimethamine 25 mg tablets 6 1 Dissolution Not registeredSulphamethoxypyrazine 500mg/Pyrimethamine25mg tablets 2 - -Total 41 5
Samples Test Registration
26
3.3.2.2 Results from CENQAM
Five (35.7%) of the 14 samples tested at CENQAM, failed analysis. All the four SP samples
analyzed failed the dissolution test of pyrimethamine, although two of them were
registered. One sample (quinine dihydrochloride mixture) which was not registered, failed
to meet specified standards as it contained active ingredient below the required amounts
(Table 12).
3.3.2.3 Comparison of Results from NQCL and CENQAM
Only about a quarter of samples that were analyzed at NQCL were also analyzed at
CENQAM. The five samples that failed analysis at NQCL were not part of the samples sent
and analyzed at CENQAM.
Although 5 samples failed analysis in each laboratory, the majority were similar batches.
Of the 43 unique batches tested in either laboratory, the overall number of failures was
16% (7 batches). Out of the fourteen samples analyzed at CENQAM, 12 were of the same
batches as those analyzed at NQCL and two (sulphadoxine-pyrimethamine tablets) were
from the same manufacturer, but of different batches. Of the 12 same-batch samples, 8
passed all tests performed at both NQCL and CENQAM (Annexes 3 and 4). One quinine
dihydrochloride injection failed on the content of active ingredient and two SP batches
failed on dissolution of pyrimethamine at CENQAM, but passed at NQCL. One batch of
quinine bisulphate mixture failed on content at NQCL, but passed at CENQAM. At both
laboratories, SP tablets from the same company but of different batches failed the
dissolution test of pyrimethamine.
Table 12: Quality control results from CENQAM
Medicine Samples Samples Tested Failed (for failed batches)Artemether-lumefantrine 20/120mg tablets 1 - -Artemether 180 mg/Lumefantrine 1080 mg/60 ml suspension 1 - -Dihydroartemisin 60mg tablets 3 - -Quinine dihydrochloride 200mg/ml drops 1 - -Quinine dihydrochloride 600mg/2ml injection 1 - -Quinine bisulphate 50mg/5ml mixture 1 - -Quinine dihydrochloride 50mg/5ml mixture 1 1 Content Not RegisteredSulphadoxine 500 mg/Pyrimethamine 4 4 Dissolution 2 Registered25 mg tablets 2 Not RegisteredSulphamethoxypyrazine 500mg/Pyrimethamine 25mg tablets 1 -Total 14 5 -
Test Failed Registration
27
4 SUMMARY OF RESULTS
1. A wide range of antimalarial medicines are available in the Kenyan market. Only 27.5%
of these formulations are recommended in current national treatment guidelines.
2. The private sector has the widest range of antimalarial medicines (95%), with the
mission and public sectors also distributing a wide range of antimalarials (75% and
67.5% respectively).
3. The widespread distribution of non-recommended medicines occurs in all provinces.
Central, Eastern and Nairobi provinces have the widest medicines range (over 80%
each).
4. The first-line treatment for uncomplicated malaria, AL (tablets) was found in all the
sectors and provinces, but in only 33% of all the facilities surveyed.
5. Besides AL tablets, there are 5 other ACTs in the Kenyan market, namely: AL
suspension, Artesunate-Sulphamethoxypyrazine-Pyrimethamine, artesunate-
amodiaquine, artesunate-mefloquine and dihydroartemisinin-piperaquine (all tablets).
These ACTs are largely distributed through the private sector, but some are found to a
small extent in the mission and public sectors.
6. For the same medicine formulation, a wide range of products from different
manufacturers are found in the market.
7. Kenya, India and China are the most significant sources of origin for antimalarial
medicines in the country.
8. Of the antimalarial products found in the market, almost half (42.2%) were un-
registered.
9. The majority of unregistered antimalarials are either manufactured in Kenya or India.
10. The majority of unregistered antimalarial products found in the market, are not
recommended in the national malaria treatment guidelines.
11. The registration status of 15.2% of the antimalarial products found in the market could
not be established at the time of the study.
12. Overall, 84% of the antimalarial medicines tested passed quality control tests, with a
failure rate of about 16%.
13. Of the drugs that failed quality tests, SP tablets, artemether injection, amodiaquine and
quinine tablets are of particular concern from a malaria control perspective.
28
5 CONCLUSIONS
The widespread availability of non-standard therapies, even in the formal public sector
undermines the national malaria treatment policy. The limited availability of AL, the first-
line treatment for malaria is consistent with the timing of the current survey which was
conducted during the initial roll-out of the new policy, and prior to the nationwide
distribution and deployment of this product in the public and mission sectors; subsequent
surveys and ongoing monitoring by the MOH have shown that AL is available in over 90%
of public sector facilities. The widespread availability of quinine (the first-line treatment for
severe malaria) in the formal sector and in all provinces augurs well for malaria treatment
and is an indicator of successful distribution by MEDS and KEMSA.
This survey highlights a number of regulatory challenges given 1) the high number of
products for any given medicine, especially the more established ones such as SP and
amodiaquine, 2) the presence of unregistered products in the market 3) the presence in
the market of non-recommended malaria medicines, such as amodiaquine, pointing to a
policy-drug registration and distribution disconnect and the 4) poor quality of SP (for
intermittent presumptive treatment), quinine and artemether injection. There is a need for
a concerted effort by the PPB, MOH and stakeholders in pharmaceutical sub-sector to
strengthen post-market surveillance to protect the market and patients from the dangers
posed by medicines whose safety, quality and efficacy cannot be guaranteed.
29
6 LESSONS LEARNT
1. There have been many studies on medicines quality in Kenya, but these have not
necessarily influenced policy. Leadership of the national regulator (PPB) was crucial in
this study, and it enabled faster action on the findings. For example, PPB noted the high
proportion in the market of AMs that are not recommended in treatment guidelines, and
initiated remedial measures including:-
Discontinued registration of new oral artemisinin mono-therapies
Gave notice to manufacturers to discontinue production, distribution or sale of
products that do not conform to malaria treatment guidelines (by March 31 2008)
Set up a task force to spearhead establishment of a post-market surveillance
system for medicines quality in the country.
2. There are gaps and challenges in enforcing medicines regulation in Kenya. Capacity
building in this area is an ongoing process that requires coordinated partner support
3. There are opportunities for disease control programmes and the medicines regulator to
work together, to positively influence and mutually support public health.
4. The capacity of the WHO pre-qualified laboratory in South Africa is overstretched, and
there is need to enhance national capacity for medicines quality control.
5. There is a lack of strategic engagement on medicines regulation at the wider health
sector level, and a lack of awareness of the role and work of the medicines regulator
(PPB).
6. Access to prompt and effective treatment is a pillar of the National Malaria Strategy.
This cannot happen without an effective medicines regulatory authority. This applies to
all key public health programmes.
30
7 RECOMMENDATIONS
A) Pharmacy & Poisons Board (PPB)
1. Enforce the withdrawal of oral artemisinin monotherapies, un-registered and sub-
standard products from the Kenyan market.
2. Use the survey data to inform drug registration and pharmaceutical inspection.
3. Establish a post-market surveillance system, to curb substandard and un-
registered drugs in the market. Develop an appropriate strategy, guidelines and
implementation framework with clearly defined mandates, roles and
responsibilities.
4. Involve relevant MOH departments and implementing partners from all sectors, in
developing the post-market surveillance and other regulatory systems
5. Computerize fully data management systems for medicines registration and make
accessible information to the public to ensure that registration status of products dcan be verified at all times .
6. Enforce compliance by all stakeholders with set pharmaceutical regulations.
7. Link implementation of medicines regulation to the health sector planning and M&E
systems (NHSSP II and AOPs), to guide support by MOH and development
partners. Develop an appropriate communication strategy to raise stakeholder
awareness on the role and work of PPB.
B) Division of Malaria Control (DOMC)
1. Spearhead countrywide dissemination, promotion and enforcement of malaria
treatment guidelines and involve all partners in the health sector. Engage more fully
with the private sector to facilitate greater compliance with the guidelines.
C) Ministry of Health (MOH)
1. Advocate for and increase financial support to strengthen key pillars of medicines
regulation, in line with the health sector support framework.
2. Support strengthening of local capacity for QC testing, to avoid delays when
samples are sent outside the country. In this regard, the NQCL and other
laboratories should receive all necessary support towards attaining WHO pre-
qualification.
d The suitability of systems like SIAMED and other relevant software should be fully explored, with the necessary adaptation or development of a customized system. In this regard, MOH, WHO and other development partners should provide the necessary support.
31
D) Development Partners
1. Support the strengthening of key pillars of medicines regulation, within the
health sector support framework. Such support should encompass human
resource capacity (numbers and skills enhancement) and strengthening of
logistical infrastructure for: market surveillance, data management, QC testing
and pharmaceutical inspections.
E) MOH Disease Control Programmes (HIV, TB, Malaria, etc)
1. Establish linkages with the PPB, to address regulatory and other
pharmaceutical issues in an integrated manner. This should include:-
collaboratively developing a national post-market surveillance strategy and
system
harmonized resource mobilization for relevant medicines regulatory
functions
jointly undertaking similar surveys to guide regulatory policy for other
classes of drugs (e.g. ARVs, medicines for TB, reproductive health, non-
communicable diseases, etc)
F) Pharmaceutical Producers, Importers and Distributors
1. Withdraw all non-recommended and sub-standard antimalarial products from
the market, through reverse-logistics in the various public, mission and private
sector distribution channels.
2. Comply with PPB regulations by ensuring that:-
only recommended antimalarial products are produced and distributed in
Kenya
all medicines are duly registered and meet specified standards of quality
G) Consumers & Consumer Groups
1. Participate actively in medicines quality and regulatory issues. This includes
reporting of suspected substandard or counterfeit products to the PPB.
32
Glossary
Active pharmaceutical ingredient: The chemical substance responsible for a product's pharmacological effect.
Brand name: Name given to a pharmaceutical product by the manufacturer e.g. Camoquin is the innovator brand (trade) name for amodiaquin. Brand names may also be used for generic products (branded generics).
Dosage form: The form in which a completed pharmaceutical product is administered e.g. tablet, capsule, injection.
Drug: See Medicine
Generic medicine: A pharmaceutical product that is manufactured without a licence from the innovator manufacturer and marketed after the expiry of patent or other exclusive rights. A generic medicine may be marketed under a non-proprietary name (such as amodiaquin) or under a branded name (such as Amochin, a branded generic amodiaquin from Kenya).
Formulation: The administration form of a completed pharmaceutical product, inclusive of the strength of the active pharmaceutical ingredient per unit dose e.g. amodiaquine 200 mg tablet, sulphadoxine 250mg-pyrimethamine12.5 mg/5ml.
Innovator brand: The product that was first authorized world wide for marketing on the basis of documentation of its efficacy, safety and quality e.g. Camoquin .
International non-proprietary name (INN): A common generic name selected by designated experts , using procedures and guiding principles adopted by the World Health Assembly, for the unambiguous identification of a new pharmaceutical substance. This name is often identical to the generic name e.g. amodiaquin
Medicine: Any dosage form containing a substance approved for the prevention and treatment of a disease.
Pharmaceutical product: Any medicine intended for human use, presented in its finished dosage form, that is subject to control by pharmaceutical legislation (registered). A product may be sold under a brand name or under a generic name.
Sample: For the purposes of this study, each of the medicines found in each facility on the day of the survey was given a sample number e.g. in one facility there may have been six samples: Camoquin suspension, Camoquin tablets, Amochin tablets, unbranded amodiaquin, chloroquin injection, chloroquin tablets. Numbering of similar or different medicines from other facilities continued sequentially giving a total of 2535 samples in the 200 facilities.
33
References
1. National guidelines for diagnosis, treatment and prevention of malaria for health workers in Kenya. 2007. Ministry of Health. Nairobi, Kenya.
2. http://www.who.int/medicines/services/counterfeit/faqs
3. A. A. Amin and G. O. Kokwaro. Antimalarial drug quality in Africa. J. Clin. Pharm. Therapeut. 32(2007)112.
4. M. A. Atemnkeng, K. De Cock and J. Plazier-Vercammen. Quality control of active ingredients in artemisinin-derivative antimalarials within Kenya and DR Congo. Tropical Medicine and International Health. 12(2007)68-74.
5. C. Maponga and C. Ondari. The quality of Antimalarials. A study in selected African countries. WHO/EDM/PAR/2003.4.Geneva, Switzerland. World Health Organisation, 2003.
6. Y. Hebron, J. N. A. Tettey, M. Pournamdari and D. G. Watson. The chemical and pharmaceutical equivalence of Sulphadoxine/pyrimethamine tablets sold on the Tanzanian market. J. Clin. Pharm.Therapeut. 30(2005)575-581.
7. L. K. Basco. Molecular epidemiology of malaria in Cameroon. XIX. Quality of antimalarial drugs used for self-medication. Am. J. Trop. Med. Hyg. 70(2004)245-250.
8. A. Abdo-Rabbo, A. Bassili and H. Atta. The quality of Antimalarials available in Yemen. Malaria Journal. 4(2005)28.
9. A. M. Dondorp, P. N. Newton, M. Mayxay, W. Van Damme, F. M. Smithuis, S. Yeung, A. Petit, A. J. Lynam, A. Johnson, T. T Hien, R. Mc Gready, J.J. Farrar, S. Looareesuwan, N. P. J. Day , M. D. Green and N. J. White. Fake antimalarials in South East Asia are a major impediment to malaria control: Multinational cross-sectional survey on the prevalence of fake antimalarials. Tropical Medicine and International Health. 9(2004)1241-1246.
10. C. K. Maitai, W.M. Kofi-Tsekpo, E. Wakori, C. Wangia, L. Mkoji and I.M. Githiga. Drug quality control in Kenya-Preliminary observations. E. Afr. Med. J. 59(1982)399-403.
11. J. Ogeto, C. K. Maitai, C. Wangia, M. L. Mkoji, E. Wakori, G. K. Rutere, R. W. Mithamo, A. Ochieng' and I. M. Githiga. Practical therapeutical drug quality control in Kenya – Further observations. E. Afr. Med. J. 60(1983)438-443.
12. I. O. Kibwage, J. O. Ogeto, C. K. Maitai, G. Rutere, J. K. Thuranira and A. Ochieng. Drug quality control work in DARU: Observations during 1983-1986. E. Afr. Med. J. 69(1992)577-580.
13. K. O. Mang'era, G. K. Rutere, J. K. Thuranira, R. Mithamo, A. Ochieng', S. Vugigi, E. Ogaja and I.O. Kibwage. Drug quality control work at Drug Analysis and Research Unit: Observations during 1987-1990. Pharm. J. Kenya. 4(1992)66-69.
14. I. O. Kibwage, J. K. Thuranira, L. Gathu, I. M. Githiga, J. M. Nguyo, J. K. Ngugi and O. King'ondu. Drug quality control work in Drug Analysis and Research Unit: Observations during 1991-1995. East Cent. Afr. J. Pharm. Sci. 2(1999)32-36.
15. G. N. Thoithi, K. O. Abuga, J. M. Nguyo, G. Mukindia, O. King'ondu, J. K. Ngugi and I. O. Kibwage. Drug quality control in Kenya: Observations in Drug Analysis Research Unit during the period 1996-2000. East Cent. Afr. J. Pharm. Sci. 5(2002)28-32.
16. I. O Kibwage and J. K. Ngugi. Sulphadoxine/pyrimethamine tablet products on sulphadoxine/pyrimethamine tablet products on the Kenyan market : Quality concerns. East Centr. Afr. J. Pharm.Sci 3(2000)14-19.
17. A. A. Amin, R. W. Snow and G. O. Kokwaro. The quality of sulphadoxine-pyrimethamine and amodiaquine products in the Kenyan retail sector. J. Clin. Pharm. Therapeut. 30(2005)559-565.
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18. A. A. Amin, D. A. Hughes, V. Marsh, T. O. Abuya, G. O. Kokwaro, P. A. Winstanley, S. A. Ochola and R. W. Snow. The difference between effectiveness and efficacy of antimalarial drugs in Kenya. Tropical Medicine and International Health. 9(2004)967-974.
19. A. A. Amin and R. W. Snow. Brands, costs and registration status of antimalarial drugs in the Kenyan retail sector. Malaria Journal. 4(2005)36.
20. A survey of medicine prices in Kenya. Ministry of Health, Kenya, Health Action International Africa and World Health Organisation. Nairobi, Kenya. 2004.
21. Medicine Prices: A new approach to measurement WHO/EDM/PAR/2003.2. Geneva, Switzerland. World Health Organisation and Health Action International. 2003.
22. Survey of the quality of antiretroviral medicines circulating in selecting in selected African countries.WHO/PSM/QSM/2007.9. Geneva Switzerland. World Health Organisation. 2007.
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Annexes
Annex 1: Data Collection Form
ANTIMALARIAL MEDICINE DATA COLLECTION FORM
Use one form for each health facility and medicine outlet
Date: Area number:
Name of town/Village/District:
Name of Health facility/Pharmacy (Optional):
Health facility/Pharmacy ID (mandatory):
Distance in km from nearest town (Population>50,000):
Type of facility:
Public
Private retail pharmacy
Mission
Other (please specify)
Name of manager of the facility:
Name of person(s) who provided the information on medicines (if different)
Data collectors:
Verification:
To be completed by the area supervisor at the end of the day.
Signed:
Date:
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Annex 1. Data collection form ……………………………………………Continued
ANTIMALARIAL DATA COLLECTION FORM
A B C D E F G H Available Tick for Name facturer Of size number Yes Origin foundAmodiaquine suspension 50 ml/5mlAmodiaquine tablet 200 mgArtemether injectionArtemether tabletsArtemether/Lumefantrine tabletsArtesunate injectionArtesunate suppositoriesArtesunate tablets/capsulesArtesunate/AmodiaquineArtesunate /MefloquineAtovaquone-Proguanil tablets (Adult)Atovaquone-Proguanil tablets (Paediatric)Chloroquine syrupChloroquine injectionChloroquine tabletsDihydroartemisinin satchetDihydroartemisin tabletsDihydroartemisinin-Piperaquine tabletsDoxycycline tablets/capsulesHalofantrine suspensionHalofantrine tabletsMefloquine tabletsProguanil tablets 100 mgQuinine dropsQuinine injectionQuinine suspensionQuinine tabletsSulphadoxine/Pyrimethamine dropsSulphadoxine/Pyrimethamine injectionSulphadoxine/Pyrimethamine suspensionSulphadoxine/Pyrimethamine tabletsSulphamethoxypyrazine/Pyrimethamine suspensionSulphamethoxypyrazine/Pyrimethamine tablets
Brand Manu- Country Pack Batch Comments
sS
Annex 2: List of Pre-selected Medicines for Laboratory Analysis
1. Amodiaquin
2. Artemether
3. Artesunate
4. Artemether/Lumefantrine
5. Dihydroartemisinin
6. Halofantrine
7. Sulphadoxine/pyrimethamine
8. Quinine
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Annex 3: Drugs Analyzed at the National Quality Control LaboratoryMedicine Samples Test Method CompendiaAmodiaquine hydrochloride 50 mg/5ml suspension 3 Microbial load Plate count BP 2002 II
Assay UV USP29NF24-AAmodiaquine hydrochloride 200 mg tablet 9 Weight uniformity Weight BP 2002 II
Dissolution UV USP29NF24Assay UV USP29NF24
Artemether 80 mg/ml injection 2 Sterility Filtration* BP2002 IIAssay HPLC IP Vol.5
-Artemether 100g/ml injection 1 Sterility Filtration* BP2002 IIAssay HPLC IP Vol.5
Artemether 20 mg/Lumefantrine 120 mg tablets 1 Weight uniformity Weight BP2002 IIDissolution HPLC , UV IHAssay HPLC IH
Artemether 180 mg/Lumefantrine 1080 mg/60 ml Susp 1 Microbial load Plate count BP2002 IIAssay HPLC IH
Artesunate 50 mg tablets 3 Weight uniformity Weight BP2002 IIDissolution HPLC IHAssay HPLC IP Vol. 5
Dihydroartemisin 60 mg tablets 3 Weight uniformity Weight BP2002 IIDissolution UV IHAssay UV IH
Halofantrine 250 mg tablets 1 Weight uniformity Weight BP2002 IIDissolution LC IHAssay LC IH
Quinine dihydrochloride 200 mg/ml drops 1 Microbial load Plate count BP2002 IIAssay NAT BP1980 II A
Quinine dihydrochloride 50 mg/ml mixture 1 Microbial load Plate count BP2002 IIAssay NAT BP1980 II A
Quinine dihydrochloride 600 mg/2 ml injection 2 Sterility Filtration* BP2002 IIAssay NAT BP1980 II A
Quinine bisulphate 50 mg/ml mixture 2 Microbial load Plate count BP2002 IIAssay NAT BP1980 II A
Quinine sulphate 200 mg tablets 1 Weight uniformity Weight BP2002 IIDissolution UV BP2002 IIAssay NAT BP2002 II
Quinine sulphate 300 mg tablets 2 Weight uniformity Weight BP2002 IIDissolution UV BP2002 IIAssay NAT BP2002 II
Sulphadoxine 500 mg/Pyrimethamine 25 mg tablets 6 Weight uniformity Weight USP29NF24Dissolution HPLC USP29NF24Assay HPLC USP29NF24
Sulphamethoxypyrazine 500mg/Pyrimethamine 25mg tablets 2 Weight uniformity Weight USP29NF24
Dissolution HPLC USP29NF24Assay HPLC USP29NF24
Total 41
BP1980 II A : Method adopted from BP 1980 II. USP29NF24-A: Method adopted from USP29NF24-A. * Membrane filtration
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Annex 4: Drugs Analyzed at CENQAM
Medicine Samples Test Method CompendiaArtemether 20 mg/Lumefantrine 120 mg tablets 1 Assay, Dissolution HPLC , UV IHArtemether 180 mg/Lumefantrine 1080 mg/60 ml suspension 1 Assay HPLC IH
thDihydroartemisin 60 mg tablets 3 Assay HPLC IP 4 EdQuinine dihydrochloride 200 mg/ml drops 1 Assay NAT BP 2007Quinine dihydrochloride 600 mg/2 ml injection 1 Assay NAT BP 2007Quinine dihydrochloride 50 mg/5ml mixture 1 Assay NAT BP 2007Quinine bisulphate 50 mg/5ml mixture 1 Assay HPLC BP 2008Sulphadoxine 500 mg/Pyrimethamine 25 mg tablets 4 Assay, Dissolution HPLC USP2007Sulphamethoxypyrazine 500mg/Pyrimethamine 25mg tablets 1 Assay, Dissolution HPLC USP2007Total 14
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Annex 5: Availability of Medicines in Each Sector
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