[e-drug] Substandard and fake drugs

[Kirsten Myhr <myhr@online.no>]

E-drug: Substandard and fake drugs
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The Lancet 2001; 357 no 9272, 16 June has one editorial, one article and 
one commentary on the issue of substandard and fake drugs. The commentary 
and abstract of the article are reproduced below.
Commentary
Too much, too little, or none at all: dealing with substandard and fake 
drugs
Drug regulation generally follows public calamities. For example, the US 
Congress passed the Biologics Control Act in 1902 as a result of the deaths 
of ten children given diphtheria antitoxin contaminated with live tetanus 
bacilli. Similarly, the US Federal Food, Drug and Cosmetics Act was passed 
in 1938 after the death of 105 people from the ingestion of a brand of 
elixir of sulfanilimide formulated with diethylene glycol instead of 
propylene glycol.1,2 In the UK, the Medicines Act, 1968, followed the 
thalidomide disaster. Today, exposure to substandard or dangerous drug 
formulations is rare in many countries and generally occurs only when the 
user strays from approved drugs and takes unorthodox treatments. 
Alternative "herbal" remedies containing corticosteroids or analgesics, 
such as phenacetin, are not unusual.3-6
In this issue of The Lancet two reports show that citizens of some 
countries need to be alert when taking orthodox treatments. R B Taylor and 
colleagues analysed the contents of drugs from pharmacies in Nigeria and 
found that about half of the preparations had concentrations of the drug 
outside upper and lower pharmacopoeial limits. For many of these 
substandard drugs the discrepancies were unlikely to affect clinical 
outcomes. Antibiotics, for example, generally have wide therapeutic ranges 
and use of preparations with amounts modestly outside pharmacopoeial limits 
would be unlikely to lead to treatment failure. However, the use of a few 
of the substandard drugs could lead to substantial morbidity or death. Some 
of the antimalarial preparations had less than 25% active ingredient. Five 
samples of metronidazole suspension, and some of the pyrazinamide samples, 
contained no drug at all.
Paul Newton and co-workers report that just over a third of the samples of 
tablets labelled "artesunate" bought from shops in Cambodia, Laos, Myanmar, 
Thailand, and Vietnam, contained no drug. The researchers are correct in 
bringing to attention the grave implications of this illicit trade. The 
practice highlighted by the two studies is widespread. An earlier study in 
Cambodia7 showed that counterfeit artesunate and mefloquine preparations 
were sold widely, and dummy contraceptive pills have been reported in 
Brazil.8 Similar difficulties with counterfeit drugs have been reported 
from other countries including Myanmar, Vietnam,9 and Kenya.10 These 
findings show the breakdown of drug-regulatory control in those countries. 
In many cases the lack of a uniform content of drug suggests poor 
manufacturing techniques. Among cases in which the preparations contain no 
drug, drugs other than the claim on the label, or have consistently low 
concentrations of drug, fraud is the most likely cause.
Controlling the dissemination of substandard and fake drugs is difficult. 
About a decade ago, Nigeria spent US$68 million trying to solve this 
problem.11 Taylor and colleagues' study shows that very little progress has 
been made. Incompetent manufacturers and lack of drug-regulatory controls 
or their enforcement suggest inadequate or corrupt government. Therefore, 
when such practices are discovered, governments cannot stand idly by 
without their reputations being tarnished too.
As a first step, the expertise of reputable local manufacturers or 
international health-care organisations should be incorporated into 
training programmes for local drug manufacturers. The enforcement divisions 
of local drug-regulatory agencies should be strengthened and, if necessary, 
officers and directors changed in order to abolish fraud. To protect 
consumers, governments and purchasers should have evidence that 
quality-assurance procedures are in place and have been followed. Regular 
government-organised independent checks on the quality of marketed 
preparations should be undertaken to inform purchasers and government 
agencies. Tablet and packaging characteristics are unlikely to be reliable 
markers of authenticity in the long-term, and specific chemical analysis 
will be necessary. Price should not be the only basis by which a supplier 
is chosen. Offenders should be barred from trading and those responsible 
brought to the attention of the public and the law. Public-education 
campaigns to draw attention to fake products should be increased. Drug 
companies making genuine products can of course also help by considering 
affordability in their pricing strategies, and so make fraud less profit  
able. Although optimism is hard to come by in this area, there is hope that 
the combination of these efforts may yield some success.
Alain Li Wan Po
Centre for Evidence-Based Pharmacotherapy, Aston University, Aston 
Triangle, Birmingham B4 7ET, UK (e-mail:a.liwanpo@aston.ac.uk)
1 Geiling EMK, Cannon PR. Pathogenic effects of elixir of sulfanilimide 
(diethylene glycol) poisoning. JAMA 1938; 111: 919-26.
2 Wax DM. Elixirs, diluents and the passage of the 1938 Federal Food, Drug 
and Cosmetics Act. Ann Intern Med 1995; 5: 456-61.
3 Ho RJ. Adulterants in Asian patent medicines. N Engl J Med 1998; 339: 
847.
4 Vander Stricht BI, Parvais OE, Vanhaelen-Fastre RJ, Vanhaelen MH. 
Remedies may contain cocktail of active drugs. BMJ 1994; 308: 1162.
5 Rubin BK, LeGatt DF, Audette RJ. The Mexican asthma cure: systemic 
steroids for gullible gringos. Chest 1990; 97: 959-61.
6 Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355: 134-38.
7 Rozendaal J. Fake antimalaria drugs in Cambodia. Lancet 2001; 357 no 
9259: 890.
8 Csillag C. Epidemic of counterfeit drugs causes concern in Brazil. Lancet 
1998; 352 no 9127: 553.
9 Wondemagegnehu E. Counterfeit and substandard drugs in Myanmar and 
Vietnam. Geneva: WHO, 1999. WHO/EDM/QSM/99.3.
10 World Health Organization. Counterfeit antimalarials detected--Kenya. 
WHO Pharmaceuticals Newsletter, 1997. Nos. 11 and 12.
11 Land T. Combating counterfeit drugs. Nature 1992; 355: 192.
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Lancet 2001; 357: 1933-36
Pharmacopoeial quality of drugs supplied by Nigerian pharmacies
R B Taylor, O Shakoor, R H Behrens, M Everard, A S Low, J Wangboonskul, R G 
Reid, J A Kolawole
School of Pharmacy, The Robert Gordon University, Schoolhill, Aberdeen AB10 
1FR, UK (Prof R B Taylor PhD, O Shakoor PhD, M Everard MPhil, A S Low PhD, 
R G Reid MSc); Department of Infectious and Tropical Diseases, London 
School of Hygiene and Tropical Medicine, London (R H Behrens MD); Faculty 
of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand (J 
Wangboonskul PhD); and Department of Pharmacy, University of Jos, Jos, 
Nigeria (J A Kolawole PhD)
Correspondence to: Prof R B Taylor (e-mail:r.b.taylor@rgu.ac.uk)
Summary
Background The quality of medicines available in some less-developed 
countries is inadequate in terms of content of active ingredient. Reasons 
for the poor quality of drugs include widespread counterfeiting of 
medicines in less-developed countries, excessive decomposition of active 
ingredient as a result of high temperature and humidity, and poor quality 
assurance during the manufacture of medicinal products. Our aim was to 
investigate the quality of different drugs obtained from retail pharmacies 
in two urban areas of Nigeria, and, in instances of poor quality, to 
ascertain the reason why.
Methods We randomly collected 581 samples of 27 different drugs from 35 
pharmacies in Lagos and Abuja in Nigeria. We analysed the medicines for 
drug content by validated chromatographic methods, and compared our results 
with pharmacopoeial requirements.
Findings 279 (48%) samples did not comply with set pharmacopoeial limits, 
and this proportion was uniform for the various types of drugs tested. 
Although some preparations contained no active ingredient, most had amounts 
just outside the pharmacopoeial limits. We identified samples with both too 
much and too little active drug content.
Interpretation The most probable cause of the poor quality of drugs is 
absence of adequate quality assurance during manufacture. Substandard drugs 
sold in the pharmacies of less-developed countries could contribute to 
global microbial resistance and therapeutic failure of infectious diseases. 
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