COUNTERFEITING OF COUNTERFEITING OF DRUGS AND THE DRUGS AND THE NECESSITY OF QC NECESSITY OF QC

SYSTEMS IN DEVELOPING SYSTEMS IN DEVELOPING COUNTRIES:COUNTRIES:

THE KENYAN EXPERIENCE THE KENYAN EXPERIENCE

ByBy

Isaac O. KibwageIsaac O. Kibwage

Authors:Authors:

G.N. ThoithiG.N. Thoithi11, K.O. Abuga, K.O. Abuga11, H.K. , H.K. ChepkwonyChepkwony2 2 andand I. O. Kibwage*I. O. Kibwage*

11Department of Pharmaceutical Department of Pharmaceutical Chemistry, Chemistry, University of University of Nairobi,Nairobi, Kenya.Kenya.

22National Quality Control Laboratory National Quality Control Laboratory (NQCL), (NQCL), Nairobi, KenyaNairobi, Kenya

Quality of MedicinesQuality of Medicines

Quality of medicinesQuality of medicinesImpact of quality on consumersImpact of quality on consumersKenyan mass media reports – Kenyan mass media reports –

drug quality concernsdrug quality concernsPoor quality Poor quality Expired products Expired products CounterfeitsCounterfeits

Lack of adequate policyLack of adequate policyLimited market surveillanceLimited market surveillance

Daily Nation, Monday May 2, Daily Nation, Monday May 2, 19881988

PSK Symposium1988:

Debate on quality of locally produced medicines stopped by PSK chairman

Kenya Times, Tuesday May 3, Kenya Times, Tuesday May 3, 19881988

Africa Health Market Letter, Vol. 6 Africa Health Market Letter, Vol. 6 No. 4, April 1992No. 4, April 1992

VLIR, KUL – UON Project for QC of drugs

Sale of non-registered loperamide & sulfadoxine/pyrimethamine in the Kenyan market.

Chief pharmacist admitted dispensing malpractices and the presence briefcase imports in the country

Sunday Standard, Nov. 9, 1997Sunday Standard, Nov. 9, 1997

Sale of non-registered loperamide & sulfadoxine/pyrimethamine in the Kenyan market.

Chief pharmacist admitted dispensing malpractices and the presence briefcase imports in the country

Sunday Standard, Nov. 9, 1997Sunday Standard, Nov. 9, 1997

Specialties authorized for the Specialties authorized for the Kenyan market:1982-2007Kenyan market:1982-2007

CategoryCategory Number of Number of SpecialtiesSpecialties

Total RegisteredTotal Registered 1957019570

Newly Newly Registered Registered

Drugs in 2007Drugs in 2007643643

Re-registered in Re-registered in 20072007 11261126

Historical Background Historical Background

DARU:DARU: Established in 1977Established in 1977

Work started in1980Work started in1980

VLIR funded KUL-UoN project was VLIR funded KUL-UoN project was a a major boostmajor boost

NQCL:NQCL: Established in 1993Established in 1993

Takeoff slow - inadequate facilitiesTakeoff slow - inadequate facilities

2004 – Enhanced budgetary 2004 – Enhanced budgetary allocation allocation + donor funding+ donor funding

WHO certification in the processWHO certification in the process

Central Medical StoresCentral Medical StoresGovernment and Private HospitalsGovernment and Private HospitalsPharmaceutical industryPharmaceutical industryPharmacy and Poisons BoardPharmacy and Poisons BoardCommunity PharmaciesCommunity PharmaciesDoctors, Dentists and patientsDoctors, Dentists and patients

Sources of DrugsSources of Drugs

Sources of DrugsSources of Drugs

1.1. Local ManufacturersLocal Manufacturers2.2. ImportedImported

IndiaIndia ChinaChina IsraelIsrael Far EastFar East Western/ Eastern EuropeWestern/ Eastern Europe

Results for DARUResults for DARUPeriod: 1980 - 2007Period: 1980 - 2007

Jan Jan 1980-1980-Jun Jun 19811981

Jul Jul 1981-1981-Dec Dec 19821982

1981983-863-86

1981987-907-90

1991991-951-95

19961996--20002000

2002001-051-05

2002006-076-07

Number Number of drugs of drugs analyzedanalyzed

182182 191191 379379 127127 262262 261261 379379 101101

Local Local drugs drugs (%)(%)

6565 6565 7171 5454 5959 6060 3737 2424

Imported Imported drugs (%)drugs (%) 3535 3535 2929 4646 4141 4040 6363 7676

Overall Overall failed failed drugsdrugs

23.123.1 26.726.7 31.431.4 21.621.6 17.617.6 21.121.1 6.16.1 8.98.9

Results for DARUResults for DARUPeriod: 1980 - 2007Period: 1980 - 2007

Jan Jan 1980-1980-Jun-81Jun-81

Jul Jul 1981-1981-Dec-Dec-8282

1981983-3-8686

1981987-7-9090

1991991-1-9595

1991996-6-20020000

2002001-1-0505

2002006-6-0707

Local Local drugs drugs failure (%)failure (%)

-- 5151 4646 2424 2020 2525 99 00

Imported Imported drugs drugs failure (%)failure (%)

-- 1515 3131 2020 1414 1616 55 16.716.7

Results for DARUResults for DARUPeriod: 1980 - 2007Period: 1980 - 2007

Jan Jan 1980-1980-Jun-81Jun-81

Jul Jul 1981-1981-Dec-Dec-8282

1981983-863-86

19871987-90-90

1991991-951-95

19961996--20002000

2002001-051-05

2002006-076-07

AnalgesicAnalgesicss

20.020.0 31.331.3 9.19.1 00 00 9.79.7 -- 6.96.9

AntibioticAntibioticss

14.914.9 31.531.5 30.030.0 26.226.2 18.418.4 10.710.7 3.23.2 55.455.4

Anthel-Anthel-

minthicsminthics-- -- 14.314.3 00 25.025.0 37.537.5 10.010.0 3.03.0

AntimalariAntimalarial drugsal drugs -- 14.314.3 6.76.7 00 2323 27.727.7 26.926.9 10.910.9

Therapeutic categories (% Therapeutic categories (% Failure)Failure)

Results for DARUResults for DARUPeriod: 1980 - 2007Period: 1980 - 2007

Jan Jan 1980-1980-Jun-81Jun-81

Jul Jul 1981-1981-Dec-Dec-8282

1981983-863-86

1981987-907-90

1991991-951-95

1996-1996-20002000

2002001-051-05

2002006-076-07

Anti-TBAnti-TB 20.020.0 20.220.2 -- -- 40.040.0 00 00 --

Electro-Electro-lyteslytes 30.830.8 45.545.5 37.837.8 40.040.0 14.314.3 23.123.1 00 11

VitaminVitamins/s/mineralmineralss

-- 00 40.040.0 -- 83.383.3 33.333.3 00 --

SkinSkin 33.033.0 58.058.0 56.356.3 67.767.7 41.741.7 25.025.0 33.333.3 --

Failure Rate for Analgesics (%)Failure Rate for Analgesics (%)

0

5

10

15

20

25

30

35

1980-1981

1981-1982

1983-1986

1987-1990

1991-1995

1996-2000

2001-2005

2006-2007

Failure Rate for Antibiotics (%)Failure Rate for Antibiotics (%)

0

5

10

15

20

25

30

35

1980-1981

1982 1983-1986

1987-1990

1991-1995

1996-2000

2001-2005

2006-2007

Failure Rate for Antimalarial Failure Rate for Antimalarial Drugs (%)Drugs (%)

0

5

10

15

20

25

30

1980-1981

1982 1983-1986

1987-1990

1991-1995

1996-2000

2001-2005

2006-2007

Failure Rate for Antitubercular Failure Rate for Antitubercular Drugs (%)Drugs (%)

0

5

10

15

20

25

30

35

40

1980-1981

1982 1983-1986

1987-1990

1991-1995

1996-2000

2001-2005

2006-2007

Failure Rate for Skin Preparations Failure Rate for Skin Preparations (%)(%)

0

10

20

30

40

50

60

70

1980-1981

1981-1982

1983-1986

1987-1990

1991-1995

1996-2000

2006-2007

ObservationsObservations

•2001-2007: Quality of drugs has improved 2001-2007: Quality of drugs has improved •Failure rate slightly higher in locally Failure rate slightly higher in locally manufactured drugs manufactured drugs•Drugs of greatest concern Drugs of greatest concern

1980 – 1990: skin preps (1980 – 1990: skin preps (50% failure)50% failure)nutritional preps (25-38%) nutritional preps (25-38%)

antibiotics (about 30%).antibiotics (about 30%).

1996-2007: antimalarials, especially S/P 1996-2007: antimalarials, especially S/P (30%)(30%)

Possible Reasons for Improved Possible Reasons for Improved QualityQuality

• Improved technology globallyImproved technology globally

• Professional advice given to local Professional advice given to local industry following failure of their products.industry following failure of their products.

•Investment in QC LabsInvestment in QC Labs

• More pharmacists in the industry More pharmacists in the industry

• Greater vigilance by the regulatory Greater vigilance by the regulatory authority.authority.

Results for NQCLResults for NQCLPeriod: 1996 - 2007Period: 1996 - 20071996-1996-20012001

2002-2002-20032003

2004-2004-20052005

2006-2006-20072007

Number of Number of drugs analyzeddrugs analyzed 101101 442442 11391139 955955

Local drugs (%)Local drugs (%) 4141 4040 27.227.2 28.228.2

Imported drugs Imported drugs (%)(%) 5959 6060 72.872.8 71.871.8

Overall failed Overall failed drugsdrugs 30.830.8 27.127.1 12.612.6 1515

Local drugs Local drugs failure (%)failure (%) 22.722.7 3232 18.718.7 23.823.8

Imported drugs Imported drugs failure (%)failure (%) 34.934.9 23.923.9 10.410.4 11.511.5

Results for NQCLResults for NQCLPeriod: 1996 - 2007Period: 1996 - 2007

Therapeutic categories (% failure)Therapeutic categories (% failure)

1996-20011996-2001 2002-2002-20032003

2004-2004-20052005

2006-2006-20072007

AnalgesicsAnalgesics 5050 16.716.7 12.312.3 17.517.5

AntibioticsAntibiotics 24.324.3 19.919.9 9.49.4 17.317.3

AnthihelmithicsAnthihelmithics 00 33.333.3 17.917.9 1010

AntimalarialsAntimalarials 14.314.3 38.838.8 20.620.6 13.813.8

Anti-TBAnti-TB 3030 38.938.9 46.546.5 17.417.4

ElectrolytesElectrolytes 16.716.7 00 2525 00

Vitamins/MineralsVitamins/Minerals -- 00 36.736.7 2525

Failure Rate for Analgesics (%)Failure Rate for Analgesics (%)

0

10

20

30

40

50

60

70

80

1996-2001 2002-2003 2004-2005 2006-2007

Failure Rate for Antibiotics (%)Failure Rate for Antibiotics (%)

1996-2001 2002-2003 2004-2005 2006-2007

Failure Rate for Antimalarials (%)Failure Rate for Antimalarials (%)

0

5

10

15

20

25

30

35

40

45

50

1996-2001 2002-2003 2004-2005 2006-2007

Failure Rate for Antitubercular Failure Rate for Antitubercular DrugsDrugs

0

5

10

15

20

25

30

35

40

45

50

1996-2001 2002-2003 2004-2005 2006-2007

ObservationsObservations

•2001-2007: Quality of drugs has improved 2001-2007: Quality of drugs has improved •Failure rate slightly higher in imported Failure rate slightly higher in imported drugs drugs•Drugs of greatest concern by end 2007Drugs of greatest concern by end 2007

antibiotics (17.3%)antibiotics (17.3%)anthelmintics (10%)anthelmintics (10%)antituberculars. (17.4%)antituberculars. (17.4%)antimalarials, (13.8%)antimalarials, (13.8%)

Counterfeit MedicinesCounterfeit Medicines

YearYear Labeled APILabeled API Found Found APIAPI

OtherOther

ParameterParameterCommentsComments

20032003Zidovidine /Zidovidine /

Lamivudine Lamivudine Zidovidine Zidovidine --

--

20042004 Amoxycillin Amoxycillin trihydrate (RM) trihydrate (RM) NoneNone -- --

20062006AmoxilAmoxil 500 500 mg capsulesmg capsules

(Amoxycillin) (Amoxycillin)

AmoxycilliAmoxycillin n

PackagingPackaging

counterfeitecounterfeitedd

Product Product failed failed dissolution dissolution and assayand assay

Counterfeit MedicinesCounterfeit Medicines

YearYear Labeled APILabeled API Found Found APIAPI

OtherOther

ParameterParameterCommentsComments

2004 2004 Caffeine Caffeine None None -- --

20052005

PanadolPanadol tabletstablets

(Paracetamol)(Paracetamol)ParacetamParacetamolol

PackagingPackaging

counterfeitecounterfeitedd

--

2007 2007 Prednisolone Prednisolone tablets tablets None None

PackagingPackaging

CounterfeiteCounterfeited d

--

Counterfeit MedicinesCounterfeit Medicines

YearYear Labeled Labeled APIAPI Found APIFound API

OtherOther

ParameterParameterCommentsComments

2004 2004

SulphamethSulphametho-o-xypyrazine/xypyrazine/

PyrimethamiPyrimethamine ne

PyrimethamiPyrimethamine only ne only -- --

2007 2007

Duo-Duo-CotecxinCotecxin tabletstablets

(Dihydroarte(Dihydroarte-misinin/-misinin/

Piperaquine) Piperaquine)

Dihydroarte-Dihydroarte-misinin onlymisinin only

PackagingPackaging

counterfeitcounterfeiteded

--

2007 2007

MetakelfinMetakelfin tabletstablets

(Sulphameth(Sulphametho-o-xypyrazine/xypyrazine/

PyrimethamiPyrimethamine ne

PyrimethamiPyrimethamine only ne only

PackagingPackaging

counterfeitcounterfeiteded

Failed assay Failed assay and and dissolutiondissolution

PREDINSOLONE TABLETS PREDINSOLONE TABLETS COUNTERFEIT (NQCL)COUNTERFEIT (NQCL)

TWO PACKS WITH THE SAME BATCH TABLETS LOOK DIFFERENT

METAKELFINMETAKELFIN TABLETS TABLETS COUNTERFEIT (NQCL)COUNTERFEIT (NQCL)

Counterfeit

Genuine product

METAKELFINMETAKELFIN TABLETS TABLETS COUNTERFEIT (NQCL)COUNTERFEIT (NQCL)

Genuine product

Counterfeit

DUO-COTECXINDUO-COTECXIN TABLETS TABLETS COUNTERFEIT (DARU)COUNTERFEIT (DARU)

Counterfeit

product

Genuineproduct

DUO-COTECXINDUO-COTECXIN TABLETS TABLETS COUNTERFEIT (DARU)COUNTERFEIT (DARU)

New product bears the hologram ‘FACT’

DUO-COTECXINDUO-COTECXIN TABLETS TABLETS COUNTERFEIT (DARU)COUNTERFEIT (DARU)

Counterfeit

Genuine product

New genuine

pack

DOU-COTECXINDOU-COTECXIN TABLETS TABLETS COUNTERFEIT (DARU)COUNTERFEIT (DARU)

Counterfeit

Genuine product

New pack

DUO-COTECXINDUO-COTECXIN TABLETS TABLETS COUNTERFEIT (DARU)COUNTERFEIT (DARU)

Counterfeit

Genuine product

New pack

The Financial Standard, Tuesday The Financial Standard, Tuesday April 20,1999April 20,1999

The People Daily, Friday August The People Daily, Friday August 6, 20046, 2004

The Financial Standard The Financial Standard May 18,1999May 18,1999

Market SurveillanceMarket Surveillance

Market Surveillance ReportsMarket Surveillance Reports

YEARYEAR LABLAB CLASS OF CLASS OF DRUGSDRUGS

AREA AREA COVERECOVERE

DD

FAILURFAILURE RATEE RATE

20002000 DARUDARU SP productsSP products Nairobi Nairobi CityCity 70%70%

1992-1992-20002000 DARUDARU Ampicillin Ampicillin

productsproducts NairobiNairobi 20%20%

20022002 NQCLNQCL AntimalarialAntimalarialss

CountryCountry

widewide29%29%

20062006 NQCLNQCL AntimalarialAntimalarialss

CountryCountry

widewide12%12%

Market SurveillanceMarket Surveillance

Market surveillance is weak in KenyaMarket surveillance is weak in KenyaConcern for qualityConcern for qualityAvailability of substandard products Availability of substandard products in the in the marketmarketRegulatory authority needs to be Regulatory authority needs to be more more stringentstringent

ConclusionsConclusions

• Counterfeits harm health, results in Counterfeits harm health, results in economic losseconomic loss

• Meaningful surveillanceMeaningful surveillance– Strong DRA Strong DRA – Well equipped QC facilitiesWell equipped QC facilities– Comprehensive policies on handling and Comprehensive policies on handling and

distribution of drugsdistribution of drugs

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS

VLIR: VLIR: EquipmentEquipment

Human resource developmentHuman resource development

Technology transferTechnology transfer

DARU: StaffDARU: Staff

NQCL: StaffNQCL: Staff

GoK, PPBGoK, PPB

Donors: GTZ, DANIDA, WHODonors: GTZ, DANIDA, WHO

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS

NATIONAL QUALITY CONTROL LABORATORY (NQCL) STAFF

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS

DRUG ANALYSIS AND RESEARCH UNIT (DARU) STAFF