Post on 15-Jan-2016
transcript
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 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.
China
India
Indonesia
Cambodia
N
EW
S
Over viewMalaria situation in CambodiaProblems faced earlier to 1999Policy of prepackaged drugs (2000)Blister packaged Artesunate and Mefloquine (ACT)Experience of blister packaging – GMP concernsChallenges of Quality assuranceCurrent Malaria Treatment PoliciesA Recent Study of Quality of Anti-Malarial DrugsStudy findings of counterfeit antimalaria drugsFuture approaches for good quality antimalaria drugsStrategy 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 minoritiesLimited accessibility to public health servicesLack of knowledge about correct treatment among risk groups and private health care providersImprecise diagnosis as poor quality microscopy persists in remote areas even in the public sector because of low salariesImproper, 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
• 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
• MOH decided to locate the packaging facility in the compound of Central Medical Store.
Antimalarial combinations currently in useTwo channels of distribution
Public Sector
Private Sector
Routine distribution system (CMS)Routine distribution system (CMS) Public HealthPublic Health ServicesServices
Commercial distributionCommercial distribution
Social marketing schemeSocial marketing schemePrivate Private Drug sellersDrug 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
• 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
Ports
Central Medical StoreAir conditioning
Storage Storage
National malaria center Air conditioningUnstable power supply
Packaging
Central Medical Store
Transport without air conditioning
Storage
National malaria center
Storage
Central Medical Store
OD pharmacy storeNo air conditioning
StorageHealth CenterNo air conditioning Patients
QC of Law materials
QC of blistersStability test
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 PoliciesPublic 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
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
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 soldTo 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
Counterfeit Antimalaria DrugsPreliminary Investigation of Quality
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)
Drug sellers in Cambodia
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
171/ 498 (~34%) drug outlets visited for collection 240 samples in 4 provinces Samples claimed to be
Results
Chinese products, 23%
Unkown origin, 15%
Cambodian products, 3.80%
Other countries , 14%
Thai products , 44%
Overall results from 3 rounds in10 districts in 4 provinces
Quinine Mefloquine Chloroquine Artesunate
Sample size
N
CFN (%)
Sample size
N
CFN (%)
Sample size
N
CFN (%)
Sample size
N
CFN (%)
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
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 meansCounterfeit drugs were found both in legal and illegal shopsNo 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
country-wide (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 !