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