Assured drug quality
Documentation, monitoring and evaluation
Regulatory elements (central administration, inspection, recall
and gov. laboratory services)
Technical elements (quality specifications, Basic tests, GMP,
GLP, GPP, GDP, GSP)
Pre-marketing quality assessment(marketing authorization/
licensing and registration)
Post-marketing authorization surveillance (for quality, adverse
events, and drug promotion)
Adequate legislation and law enforcement
Drug quality assurance structural components
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Methodological framework for monitoring
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Performing TLC test
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17 sites participatingMekong Sub-Region: Sentinel sites
Yunnan Province of PR of China LaosVietnamMang LaSayaburiLai
ChauRui LiSavannakethQuang TriChampasakDaklakBinh Phuoc
CambodiaThailandPursatMae Hong Son PailinKanchanaburi
BattambangChanthaburi/TratPreah VihearRanong
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Testing levels of current practice
Activity and requirementsLevel of testingQuantity/number of
samplesSample collectionBasic testing (physical/visual inspection,
simplified disintegration, TLC)
Sentinel siteTest: 100% of samples collected.Send: 100% doubtful
samples to NDQC or designated Lab for verification100% of failed
samples5-10% of passed samplesVerification Basic test and/or
Pharmacopeial specifications
NDQC or designated LabsTest: 100% samples received from sentinel
sites.Send: 100% doubtful samples to reference lab for
confirmation100% of failed samples, where possible5-10% of passed
samplesConfirmationPharmacopeial specification
Reference Labs
Test: all samples received from NDQC Lab/designated Lab
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General Rules for Interpreting TLC Results
This simple guideline uses the percent Rf error, defined below,
to determine the fate of a sample based on simple TLC.
Rf Sample Error = {|Rf (standard) Rf (sample)| / Rf (standard)}
x 100%
ExampleFrom multiple TLC experiments, the following Rf values
were obtained:Rf (standard) = 0.55Rf (sample) = 0.53Then, Rf Sample
Error = {(0.55 0.53)/0.55} x 100% = 3.6 %Interpretation of TLC
ResultsBased on the typical Rf values, broadness of TLC spots and
simple error analysis[1], some broad rules can be applied to
interpret TLC results. It is important to note that these rules
should only be considered semi-quantitative and not absolute.When
Rf Sample Error is 5% or less, the sample can be considered
PassWhen Rf Sample Error is 10% or more, the sample can be
considered FailWhen Rf Sample Error is between 5% and 10%, the
sample can be considered DoubtfulNote:If the TLC chamber and plates
were not well saturated, or if the saturation has been disturbed
the spots may not be horizontal and this could give high Rf sample
error.Always make TLC in duplicate and compare the Rf of both
runs.When Rf sample error is more than 5%, always make another
duplicate run under optimal conditions to double check the doubt.
[1] Quantitative Chemical Analysis, 6th Edition. Daniel C. Harris,
W. H. Freeman, New York, 2003.
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Indicators used for monitoringBackground IndicatorsProcess
IndicatorsOutcome IndicatorsImpact Indicators
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Indicators used coreOC 1: Number of batches or lots failing
quality tests that are removed from the National Malaria Program or
from the market .
OC 2: Administrative or regulatory actions taken against
providers or manufacturers that sell poor quality antimalarial
drugs
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Progress to date
ActivityCountry Verification/confirmatory testing on going
TrainingRound 1Round 2Round 3Remark CambodiaLaosThailandTo
expand to +5 sitesViet NamTo expand to +2 sitesYunnan of China
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Sentinel sites by country and No. of samples
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Preliminary data from countries
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Preliminary data from countries* Substandard (low API
content
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Summary of test results in rounds 1 & 2 Viet Nam
Round 1Round 2
Name of sitesNo. of samples collectedNo. of samples tested that
failed basic tests at sentinel sitesLai Chau210 (0%)Quang Tri152
(13.3%)Dak Lak251 (4%)Binh Phuoc140 (0%)Total753 (4%)
Name of sitesNo. of samples collectedNo. of samples tested that
failed basic tests at sentinel sitesLai Chau190 (0%)Quang Tri91
(11.1%)Dak Lak190 (0%)Binh Phuoc130 (0%)Total601(1.7%)
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Failure rates by drug in rounds 1 & 2 Viet Nam
Round 1 Round 2
Name of drug samplesNo. of samples collected/LotNo. of Lots
tested and failed using basic tests at sentinel sites or failed at
NIDQCNo. of samples collected/LotNo. of samples tested and failed
using basic tests at sentinel sites [verification test results not
yet available]Chloroquine phosphate tablet 250mg14/113 (27%)2 in
Quang Tri1 in Dak Lak15/90Quinine sulfate 250mg12/82
(25%)10/60Quinine Dihydrochloride 500mg1/1000Artesunate
50mg27/16021/161 (6.3%)(1 out of 4 Lot failed = 25% in Quang
Tri
Mefloquine 250mg5/1000Fansidar tablet (Sulf 500mg+Pri
25mg)16/10013/70Primaquine001/1-Total75/475 (10.6%)60/391
(2.6%)
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Test results summary in Cambodia
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Test results summary in Cambodia (contd)
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Test results summary in Cambodia (contd) Round 1 by drug
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Genuine artesunate hologram of Guilin Pharmaceutical
Co.Artesunate 50 mg 002-03 PVH lot 000902 of labeled as Guilin
Pharmaceutical Co.
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Genuine artesunate hologram of Guilin Pharmaceutical
Co.Artesunate 50 mg 002-03 PVH lot 000902 of labeled as Guilin
Pharmaceutical Co.
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Genuine artesunate hologram of Guilin Pharmaceutical
Co.Artesunate 50 mg 002-03 PVH lot 000902 of labeled as Guilin
Pharmaceutical Co.
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Genuine artesunate hologram of Guilin Pharmaceutical
Co.Artesunate 50 mg 071-03 PS lot 010401ot of labeled as Guilin
Pharmaceutical Co.
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Genuine artesunate hologram of Guilin Pharmaceutical Co.Found
after 1998 in Vietnam and Cambodia
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Genuine artesunate hologram of Guilin Pharmaceutical Co.Fake
found in 2002/03 in Laos and Cambodia
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Presentation outlineKey points to alert us about poor quality
medicinesAntimalarial drug quality monitoring in Mekong
Sub-RegionBrief overview of the projectProgress to datePreliminary
resultsObservation, action taken and closing remarks
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ObservationsIt is clear that poor quality antimalarial medicines
are widely available and used in all countries much to be
doneContinuing support and commitments of Governments and donors at
all levels are neededFinancially for project
sustainabilityIntegrate into GFATM activities?Law and regulations
enforcement
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Action taken by different parties USP DQIContacted Yunnan of
China (YIPD) and WPRO on 2 lot-artesunatesContacted Viet Nam NIMPE,
NIDQC and DAV In process of contacting CMPE, FDD and FDQCC of
LaosIn process of contacting CNM, FDD and NLDQC of Cambodia
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Even if these principles are followed1. Qualified / trained
health care provider consulted2. Proper diagnosis made3. STGs
followed i.e.correct drug prescribed in right dose and right route
of administration4. Objective information obtained5. Treatment
regimen compliedClosing thoughts there will be no cure if the
quality of medicines used is poor Collaborative and persistent
actions are required from the responsible authorities at local,
national and regional levels