WORKINGPAPER
PilotAssessmentoftheQualityofCiprofloxacinin
selectedLatinAmericanCities
TheresearchwasoverseenbyRogerBate,DirectoroftheSafeMedicinesCoalition.Thesampling
collectionsandmedicinetestingwerefundedbytheLegatumInstituteandtheInternationalPolicy
Network.
Summary
Ciprofloxacin was sampled from pharmacies in ten Central and South American cities. At least six per
cent of the medicines are substandard or falsified. Sao Paolo, Buenos Aires and Montevideo have very
few substandard or falsified medicines, whereas Asuncion and Caracas had considerably more. There are
possible explanations for this, such as the latter cities having more unregistered products sold in
pharmacies, but this is only a pilot study, without detailed analysis of the possible socioeconomic and
legal causes. The study also only assesses a few cities and one medicine, a more detailed assessment
would be useful to guide policymakers as to how to respond to this public health menace.
Introduction
Therehavebeenassessmentsofbasicmedicinequalityfrommanycountriesandregionsacross
theworld(IOM2013),butalmostnoneinCentralandSouthAmerica.Overthepastdecademy
colleaguesandIhavecollectedovertenthousandsamplesofmedicinesfrom22citiesin
emergingmarkets,buttheonlyonefromtheLatinregionwasSaoPaoloinBrazil.Wehavenow
rectifiedthisgap,atleastforonecriticalmedicine,thebroadspectrumantibioticciprofloxacin.
WehaveundertakenconsiderableresearchonCiprobefore(Bateetal2015,Bateetal2016),
anditistheonedrugwehavefoundineverycityandmostpharmacieswithineachcity.We
thereforeexpectedtobeabletofinditineachofthenineLatincities(inadditiontoSaoPaolo)
wesampled,whichincludedAsuncion,BuenosAires,Caracas,GuatemalaCity,Guayaquil,La
Paz,Lima,Montevideo,SaoPaoloandTegucicalpa.
Weareinterestedinidentifyingfakeorfalsifiedmedicines,thosethatarenotmadebythe
manufactureronthepackaging,andassessingwheresuchproductsoccur.Butourmainaimis
toanalyzethequalityofmedicinesmadebythelegitimatemanufacturer.Thisisbecauseour
priorresearchindicatesthat,atleastinemergingmarkets,substandardmedicinesarethe
largerthreatandonethatisarguablyeasierforpolicymakerstoaddress.Assuchtheaimofthis
paperistoidentifyanysubstandardmedicinesineachcity,assesswheretheyaremade,and
whethertheyareregisteredinthecountryofpurchase.Thefindingswillthereforebe
comparablewithpriorresearch,butnovelbecausemostLatincountrieshaveneverbeen
assessedinthisway.
Method
Weinstructedcovertshoppersfromtheregiontorandomlywalkintopharmaciesandclaim
thatafamilymemberneededaspecifictypeofdrug.Tomimicrealpatientsasmuchas
possible,thecovertshoppersdidnotpresentadoctor’sprescriptionandalwayspurchasedthe
pharmacist-suggestedbrand.Informaldrugvendors(busvendors,mobilecarts,etc.)occurin
somelocations,buttobeabletocompareacrossalllocations,ourshoppersonlyvisited
pharmacieswitharegularstorefront.Asaresult,oursamplesarelikelytounderstatethe
problemofpoor-qualitydrugs,giventheexpectationandexistingevidencethatinformal
vendorssellworsedrugs(IOM2013).
AllmedicineswereassessedfollowingtheGlobalPharmaHealthFund(GPHF)e.V.Minilab®
protocoltoidentifysubstandardorfalsifiedmedicines(Jahnkeetal,2001).Thekeytestforour
sampleisthesemi-quantitativethin-layerchromatography(TLC),whichassessesthepresence
andconcentrationofactiveingredientinatestsampleascomparedtothereferencestandard.
AsampleisreferredtoasfalsifiedifitcontainszerocorrectAPI,andreferredtoassubstandard
ifitcontainssomecorrectAPIbuttheamountofAPIisunder-dosed(below80%).This
techniquehasbeenusedforthepastdecadebyourteamineverysampling.Alltestswere
conductedwithin60daysafterpurchase,followingtheclassificationinBate,JinandMathur
(2015).
ItisimportanttonotethatmedicinescanbesubstandardandstillpassTLC,sincetheymaynot
besolubleorbepoorlyformulatedinotherways.Asaresultourassessmentsarelikelyto
underestimatethenumberofpoorqualitymedicines.
Asacknowledgedinotherstudies(Attaranetal2012),thelegaldistinctionbetweenfalsified
andsubstandardproductsisoneofintention:bothsortsofcompromisedmedicinesarenotas
labeledandviolatetherelevanttechnicalstandards,butsubstandardmedicinesare
compromisedaccidentallyornegligently,whilefalsifiedmedicinesarecompromised
intentionally,withthisdifferencenotalwaysbeingapparentfromthecontentofthemedicine.
Inotherwords,legallyspeaking,falsifiedproductsaretheproductoforganizedcriminalintent,
butsubstandardmedicinesarewrongfullyproducedbyotherwiselegitimate,law-abiding
manufacturers.However,thislegaldistinctionbreaksdownwhenalegitimatemanufacturer
intentionallycheatsontheingredientsofthemedicine.Inlightofthedifficultytodetectthe
intentofmanufacture,thispaperdistinguishessubstandardandfalsifieddrugsbyAPIonly.
Results
Astable1belowshows,513samplesofciprofloxacinwereboughtintencities(SaoPaolowas
sampledtwice,thefirsttimein2012).Overall6.3%(33/518)ofthemedicinesfailbasicquality,
oftheseten(1.9%)wereobviousfakesand23(4.4%)weresubstandard.
Fivecitieshadnoobviousfakemedicines,Ascuncion(4/547.4%)andCaracas(2/424.7%)had
morefakesthantheothercities.OnlyBuenosAireshadnofailingmedicinesatall(nofalsified
medicinesandnosubstandards).Caracashadthemostsubstandardmedicines(4/42,9.5%).
Table1
City
SaoPaolo2012
SaoPaolo2016
Guayaquil
Lima
Tegucicalpa
GuatemalaCity
LaPaz
Ascuncion
BuenosAires
Montevideo
Caracas
Total
failing Fake
Samples
70
42
43
55
44
52
33
54
44
39
42
518
Fail%
3
1
2
4
3
4
2
7
0
1
6
1
0
0
1
1
1
0
4
0
0
2
33 10 %
Substandard
Fake%
4.28
2.38
4.65
7.27
6.81
7.69
6.06
12.96
0
2.56
14.28
6.37 1.43
0
0
1.82
2.27
1.92
0
7.40
0
0
4.76
1.93
2.86
2.38
4.65
5.45
4.54
5.77
6.06
5.55
0
2.56
9.52
%
Registered Registered
4.44
66
41
38
50
37
44
30
38
41
37
29
94.28
97.62
88.37
90.91
84.09
84.61
90.91
70.37
93.18
94.87
69.05
451 87.06
Removingthetenfakemedicinesfromthesample,wherebydefinitionwedonotknowwhere
theyweremade,thelocationofproductionofthelegitimatemedicineisintable2below.The
largestsupplierofCiprotoallLatincountriesisIndia,providing35%(179/508)ofthesample.
ProductsmadeinLatinAmerica(whethermadedomesticallyinthecountryofpurchaseor
imported)provide159(31%)samplesandEurope,USandotherOECDnationsprovidethenext
mostat90(18%).OECDmedicinesdidnotfailatall,whereasIndianandChinesemedicines
bothfailedmorethanotherlocationsatover6%ofthesample.
Approximately87percentofthemedicineswereregisteredinthecountryinwhichtheywere
procured,butthisbeliedarangeof97%inSaoPaolodownto70%inCaracasandAsuncion.
Thesamplesizesaretoosmalltodeterminestatisticallywhetherunregisteredproductsfailed
moreoften,however,inCaracasthreeofthefoursubstandardproductswereindeed
unregistered.
Table2
Production
location
Domestic
India
China
OECD
OtherLatam
Samples Substandards
71
179
80
90
88
508
2
12
5
0
4
23
%fail
2.81
6.70
6.25
0
4.54
4.52
Discussion
Itisinterestingtocomparethesenewresultswithpreviousresultsfrompriorpapers.Inour
largeststudyofciprofloxacin(Bateetal2015)wefoundthat83outof1437samplesofCipro,
roughly5.8%ofsamples,weresubstandard.Thisisaslightlyhigherpercentagethanfoundin
thislatestresearch(4.5%).Thediscrepancyismostlikelyexplainedbythefactthatjustover8%
ofthesampleboughtinAfricancitiesfailed,whereastheratewascloserto4%inmid-income
emergingmarkets(includingIndiancitiesandtheoriginalSaoPaolosampleof2012).Inthat
respectthesenewdataareconsistentwithpreviousdata.
Alsoconsistent,thoughnotanalyzedindetail,isthatrichercitiestendtohavebetterquality
medicines,aswesawinBateetal2015andBateetal2016.BuenosAires,SaoPaoloand
MontevideoareamongtherichercitiesandAsuncionandCaracasamongthepoorerandtheir
qualityresultsreflectthat.AsuncionandCaracasalsohavethefewestregisteredproducts,and
previousresearch(Bateal2015andBateetal2016)showsthatunregisteredproductsare
morelikelytofailqualitycontrolandsuchnationsareassociatedwithmorefalsifiedmedicines.
Insummary,LatinAmericancitieshavemoreregisteredCiproanditisofbetterqualitythan
Africancities,butmarginallyworseresultsbycomparisonwithothermid-incomenationcities
analyzedpreviously.
Conclusion
TenCentralandSouthAmericancitieshadciprofloxacinsampledfromlocalpharmacies.
Approximately6.3%failedaverybasicqualitythinlayerchromatographytest,providinga
minimumassessmentofsubstandardandfalsifiedciprofloxacinmedicinesonthemarket.There
wasquiteavarietyinperformanceofthecities,withSaoPaolo,BuenosAiresandMontevideo
haveveryfewsubstandardmedicines,whereasAsuncionandCaracashadconsiderablymore.
Thisisonlyapilotstudylookingatafewcitiesandonemedicine,amoredetailedassessment
wouldbeusefultoguidepolicymakersastohowtorespondtothispublichealthmenace.
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