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.
References
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