Transcript cambodian nattional malaria treatment policy

Cambodian experiences on quality of
antimalarial medicines
Dr. Duong Socheat,
National Malaria Centre, Cambodia
Workshop on GMP and Quality Assurance of Antimalarial
Medicines for WHO/SEARO and WHO/WPRO regions
18-22 October, Bangkok, Thailand
Location of Cambodia
The Kingdom of Cambodia shares its borders with Thailand and
Laos on the north, with Vietnam on the East and South, and with
the Gulf of Siam and Thailand on the South and West.
China
N
India
W
E
S
Cambodia
Indonesia
Over view
Malaria situation in Cambodia
Problems faced earlier to 1999
Policy of prepackaged drugs (2000)
Blister packaged Artesunate and Mefloquine (ACT)
Experience of blister packaging – GMP concerns
Challenges of Quality assurance
Current Malaria Treatment Policies
A Recent Study of Quality of Anti-Malarial Drugs
Study findings of counterfeit antimalaria drugs
Future approaches for good quality antimalaria drugs
Strategy of Drug Quality Assurance in Pharmaceutical
Development
Malaria Situation in Cambodia
High malaria occurrence among migrants, casual
workers during harvest season, forest workers, gem
miners, road construction workers, soldiers,and ethnic
minorities
Limited accessibility to public health services
Lack of knowledge about correct treatment among risk
groups and private health care providers
Imprecise diagnosis as poor quality microscopy
persists in remote areas even in the public sector
because of low salaries
Improper, inadequate, expensive and ineffective
treatments including counterfeit drugs in the private
sector
HISTORICAL
PERSPECTIVE
• Malaria, a major scourge in Cambodia for several decades.
• Monotherapy mainly followed until 1999
- 1993: Shifted from Chloroquine to Quinine + Tetracycline
- 1994: Changed from Quinine + Tetracycline to Mefloquine
• Combination therapy recommended for the first time in
1999 -Artesunate and Mefloquine (without packaging)
• Treatment guidelines revised in 2000 introducing
prepackaging of Artesunate and Mefloquine
• Further revisions are due depending on the outcomes of
current research underway
Problems accumulated until 1999
(which prompted the shift to Combination therapy)
1. Increasing levels of multi drug resistance
especially in border areas with Thailand
2. Huge burden of counterfeit or low quality
antimalarial drugs in the open market
3. Inappropriate prescription practices in the
private sector
4. Inappropriate treatment seeking behavior
and drug use
Reasons for pre-packaging
by the National Programme
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Necessity to stabilize drug resistance, control
counterfeit drugs, and improve drug use of
antimalaria drugs for both providers and patients
Particular response requirements to the malaria
burden (ACT)
Combination treatment of artesunate and mefloquine
was not commercially available
Local pharmaceutical manufacturers were not ready
for blister-packaging with GMP standard
Malaria Program need to provide ACT in blister to
assure proper use for both public and private sector
Policy of pre-packaged drugs (2000)
• The Sub-Cocom of Ministry of Health declared
the country’s malaria treatment policy:
• A combination of Mefloquine® + Artesunate® is the
first line treatment for uncomplicated Pf malaria
• The regimen have to be pre-packaged in different
age/weight groups
- decided to locate the packaging facility in
• MOH
the compound of Central Medical Store.
Antimalarial combinations currently in use
Two channels of distribution
Public Sector Routine distribution system (CMS)
Private Sector
Commercial distribution
Social marketing scheme
Public Health Services
Private Drug sellers
Advantage of pre-packaged drugs
• To improve or stabilize resistance levels:
– Standardized and effective treatment nationwide
– Combination of artesunate and mefloquine
• To improve the patient’s compliance
– Short duration of treatment
– Pre-packaged treatment
• To improve the patient’s understanding of the
treatment administration
– User friendly IEC approach (outer box and
instruction notice)
Experiences of production
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Ministry of Health agreement / WHO’s support
Determine required equipment
Design moulds for blistering
Develop packaging unit
Train workers
Import raw materials like aluminum foil and
PVC as well as drugs
• Maintain program to supply drugs on time
Good Manufacturing Procedures concerns
• Quality assurance issues have been addressed
• Cambodia GMP guidelines was published in 2000
• Constant monitoring system for GMP / Routine
inspection to manufacturers is under development
• Specifications for raw materials must be robust
– Obstacles encountered during procurement process
• Management of the packaging plant must be
comprehensive in order to be efficient and effective
• Concerns with the GMP criteria for drugs and other raw
materials
– No pre-qualified mefloquine is available
Challenges of Quality Assurance of
blister packaging A+M
Storage
Ports
Storage
Central Medical Store
Air conditioning
Packaging
QC of
Law materials
National malaria center
Air conditioning
Unstable power supply
QC of blisters
Stability test
Central Medical Store
Storage
OD pharmacy store
No air conditioning
Storage
National malaria center
Health Center
No air conditioning
Transport without air conditioning
Storage
Central Medical Store
Patients
Results of A+M quality
•Before blister package:
–Mefloquine 250 mg from Denmark : Conform to specification
–Artesunate 50 mg from China : Conform to specification
–Artesunate 50 mg from Vietnam : Problem of Friability
•After blister package:
–A+M4: Conform to specification
•Quality after 3 month in the field
– A+M4: Conform to specification
•Stability tests for A+M and Malarine was conducted and passed
Current Malaria Treatment Policies
Public Sector
 Treatment guidelines for 3 Day combination therapy using
mefloquine and artesunate after obligatory use of rapid diagnosis
test or microscopy
 Pre-packaging and distribution of dipsticks and anti-malarial
combination treatment for hospitals & health centers free of
charge
Private Sector
 Social Marketing of Rapid Diagnostic Test & a brand-named prepackaged combination therapy
 Health Education through advertisement of the product on Mass
Media
Village Malaria Workers
 I male and I female villagers are trained for RDT and ACT
 300 villages will be covered under GF round 2
Handing over of Blister packaging of A+M to
pharmaceutical manufacturer
•Cambodia Pharmaceutical Enterprise (CPE) has been
established since 1999
•MOU between the National Malaria Centre and the
Cambodia Pharmaceutical Enterprise (CPE) in May 2004
•Renovation of Blister Packaging Room
•Australia Business Volunteers for GMP Jan, 2005
(Training manager of GMP and Quality Assurance, Abbott Australia)
•CPE will start blister-packaging for A+M early 2005
Counterfeit Antimalaria Drugs
Preliminary Investigation of Quality
1. To obtain and document evidence-based data from the field
on the quality of selected antimalarial drugs in Cambodia
To quantify fake antimalarials using MiniLab technology
along Thai border areas
To assess the prevalence of drug shops where fake antimalaria drugs are sold
To increase skills of provincial health staff in research
methodology including sample collection, analysis using
MiniLab, and reporting
2. To present suggestions to policy-marker on developing and
implementing appropriate strategies to address the drug
quality problems
Drug sellers in Cambodia
There are 3 kinds of legal drug shops in the country
Pharmacy= responsible by Pharmacist, 393
Depot A= responsible by assistant Pharmacist, 175
Depot B = responsible by retired midwives or nurses, 446
Illegal drug outlets in Cambodia, 2461
(Department of Drug and Food, 2002)
Sites for preliminary study
10 Operational Districts in 4 provinces
No. of outlets
in the 4 provinces
–23 Pharmacies
–12 Depot A
–72 Depot B
–391 illegal drug outlets
Results
171/ 498 (~34%) drug outlets visited for collection 240
samples in 4 provinces
Samples claimed to be
Cambodian
products, 3.80%
Other countries ,
14%
Unkown origin, 15%
Thai products , 44%
Chinese products,
23%
Overall results from 3 rounds
in10 districts in 4 provinces
Quinine
Mefloquine Chloroquine Artesunate
Sample CF
size
N (%)
N
Sample CF
size
N (%)
N
85
46
61*
72%
Sample CF
size
N (%)
N
3
93
6.5%
Sample CF
size
N (%)
N
7
92
0.1%
CF: Counterfeit drugs
* Brainy: unidentified manufacturer
**Sophisticated counterfeit of Guilin artesunate blister
18**
20%
Summary of the study findings
 The burden of fake antimalarials is significant
 Impossible to determine the source of the counterfeit drugs
 Difficult to identify counterfeit drugs by visual means
Counterfeit drugs were found both in legal and illegal shops
No counterfeit drugs were found in registered drugs sampled
Drug registration appears important to reduce problems
 Anecdotal evidence
Community awareness campaigns appeared to have some
beneficial outcomes – TV campaign for “Brainy drugs”
Drug sellers buy drugs without knowing the quality
Main causes of the problem of counterfeit drugs
in Cambodia
• Effort has developed pharmaceutical law and
regulations, but are still weak
• The weak law enforcement
• The weak education campaign
• The poverty of Cambodian population
• The insufficient number of drugs inspectors
• The unsuccessful intervention of the MoH in
previous years due to the limited collaboration and
cooperation among concerned regulatory agencies
Future approaches for good quality antimalaria drugs
• Continued monitoring of drug resistance to guide the revision of
national drug policy
• Continued monitoring of anti-malarial drug usage
• Implementation of regular quality control of anti-malaria drugs in
the private as well as public sector (including storage conditions)
• Ensuring the adequate supplies of combination drugs in the public
and private sectors
• Strengthen procurement capacity
• Enacting legislation prohibiting the selling of non-recommended
regimens
• Building up all possible partnership networks for improving
implementation of national treatment guidelines.
• Conduct sustained community awareness campaigns
Strategy of Drug Quality Assurance
in Pharmaceutical Development
• Strengthen management of pharmaceuticals and other medical supplies by
introducing GMP, GPP, GLP, GSP and appropriate inventory system
• Improve access of consumers to appropriate good quality pharmaceuticals in
the public and private sector
• Promote the quality of prescription and dispensing and appropriate use of
drugs
• Improve attitudes of pharmaceutical service providers towards consumers for
improving communication
• Strengthen the implementation of drug policies, laws and regulations for
public safety
• Reduce potential for harm to people’s health from counterfeit, sub-standard,
poor quality and other dangerous drugs
• Strengthen Drug Quality Control
• Increase the skill of pharmaceutical workers in the private and public sector to
follow national policy and procedures and achieve desired quality of work
• Strengthen procurement and distribution of essential medical supplies countrywide (3 years rolling plan of Department of Drug and Food)
Partners
• National Center for Parasitology Entomology
Malaria Control program
• Provincial Health Departments
• National Laboratory for Drug Quality Control
• Department of Drugs and Food
• Cambodia Pharmaceutical Enterprise
• US Pharmacopoeia / Drug Quality Information
• USAID/AusAID/World Health Organization
Thank you !