CAMBODIAN NATTIONAL MALARIA TREATMENT POLICY

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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
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Location of CambodiaThe 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.
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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

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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

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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

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Problems accumulated until 1999(which prompted
the shift to Combination therapy)

• Increasing levels of multi drug resistance
  especially in border areas with Thailand
• Huge burden of counterfeit or low quality
  antimalarial drugs in the open market
• Inappropriate prescription practices in the
  private sector
• Inappropriate treatment seeking behavior and drug
  use

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Reasons for pre-packaging by the National
Programme

• 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

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Policy of pre-packaged drugs (2000)

• The Sub-Cocom of Ministry of Health declared the
  countrys 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
• MOH decided to locate the packaging facility in
  the compound of Central Medical Store.

• -

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Antimalarial combinations currently in use Two
channels of distribution
Public Sector
Routine distribution system (CMS)
Public Health Services
Commercial distribution Social marketing scheme
Private Sector
Private Drug sellers
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Advantage of pre-packaged drugs

• To improve or stabilize resistance levels
• Standardized and effective treatment nationwide
• Combination of artesunate and mefloquine
• To improve the patients compliance
• Short duration of treatment
• Pre-packaged treatment
• To improve the patients understanding of the
  treatment administration
• User friendly IEC approach (outer box and
  instruction notice)

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Experiences of production

• Ministry of Health agreement / WHOs 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

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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

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Challenges of Quality Assurance of blister
packaging AM
QC of Law materials
Storage
Storage
Ports
National malaria center Air conditioning Unstable
power supply
Central Medical Store Air conditioning
QC of blisters Stability test
Packaging
Storage
Storage
Central Medical Store
National malaria center
Central Medical Store
Storage
Health Center No air conditioning
Patients
OD pharmacy store No air conditioning
Transport without air conditioning
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Results of AM 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
• AM4 Conform to specification
• Quality after 3 month in the field
• AM4 Conform to specification
• Stability tests for AM and Malarine was
  conducted and passed

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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 pre-packaged 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

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Handing over of Blister packaging of AM
topharmaceutical 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 AM early
  2005

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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
  anti-malaria 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

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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)

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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

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Results

• 171/ 498 (34) drug outlets visited for
  collection 240 samples in 4 provinces
• Samples claimed to be

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Overall results from 3 rounds in10 districts in
4 provinces
Quinine Quinine Mefloquine Mefloquine Chloroquine Chloroquine Artesunate Artesunate
Sample size N CF N () Sample size N CF N () Sample size N CF N () Sample size N CF N ()
85 61 72 46 3 6.5 93 7 0.1 92 18 20
CF Counterfeit drugs Brainy unidentified
manufacturer Sophisticated counterfeit of
Guilin artesunate blister
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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

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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

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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

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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 peoples 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 country-wide (3 years
  rolling plan of Department of Drug and Food)

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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

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Thank you !