Bad Medicine

Trade in counterfeit drugs is a growing but illegal business worth billions of pounds a year. Jihène El Kafsi and Peter Raven examine some of the implications

There is a famous scene in the 1949 film The Third Man that illustrates the driving-force behind the counterfeit drug industry. Orson Welles, a black marketeer who has made a fortune by selling fake penicillin in occupied Vienna at the end of the second world war, is at the top of a big wheel with his friend, looking down at the people walking around on the ground below, like so many tiny dots. He asks his friend if his conscience would really trouble him if he were to be given ten thousand dollars for each dot that stopped moving.

Today the business is worth a staggering $35bn a year,¹ but for a long while the West has largely ignored the distant dots in the developing world that have stopped moving as a result of the counterfeit drug trade.

The first documented cases of counterfeit drugs date back to the 4th century BC.² However, for over 2000 years, the issue of fraudulent production of these compounds has mostly been ignored. It was only in 1985 in Nairobi that the World Health Organization adopted eradication of counterfeit drugs as a priority. More recently, it is only because fake drugs have spread insidiously from local markets to more global outlets, aided by the rise of the internet, that the developed world has recognised the magnitude of the problem.

Definitions

A recurring problem in the literature on fake drugs is the lack of agreement on a single workable definition. How can the clandestine trade be put to a halt when we don't have a clear and internationally agreed description of what constitutes a “fake drug”? The WHO definition is the most often quoted and the most adequate. A counterfeit drug is defined as a product that is deliberately and fraudulently mislabelled with respect to identity or source. Counterfeiting can apply to both branded and generic products, and counterfeit products may include products with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient active ingredient, or with fake packaging.¹

The cheap compounds substituting the active ingredients range from chalk to poisonous compounds such as antifreeze. Although counterfeit drugs may contain the correct amount of active ingredients—for example, in a case where only the packaging is fake—they remain dangerous because they originate outside any quality control system.

There is a subtle difference between fake drugs and substandard drugs. A substandard drug is one that contains no, too little, or too much active ingredient and is an ineffective treatment. Substandard drugs are considered to be in a subcategory of fake drugs, as they do not necessarily originate from criminal intent, but can simply be the result of a defective manufacturing process.¹

Global problem

The counterfeit drug trade accounts for 10% of the international pharmaceutical trade and 25% of medications used in the developing world,¹ a particular problem where vulnerability factors include poverty and weaker regulatory systems. These alarming figures are steadily rising, despite measures to combat the problem, and should be employed to raise public awareness and to educate medical personnel on fake drugs and their consequences.

As the drug counterfeiting trade has recently been targeting developed countries in Europe and North America, all doctors and medical staff should keep in mind that they may be faced with medical scenarios that can very well be linked to the use of a substandard or a fake drug.

The following are examples of the devastating effects of the fake drug trade and are evidence that this traffic has become global and closer to home than one thinks.

In the Philippines, 8% of prescription drugs are counterfeit, whereas in Cambodia, 60% of 133 drug vendors were found to be selling a fake antimalarial drug.³

Dondorp et al conducted a cross sectional survey to assess the prevalence of counterfeit antimalarial drugs in Southeast Asia by measuring the proportion of the drug artesunate in antimalarial tablets. They targeted pharmacies and shops selling antimalarial drugs in Myanmar (Burma), Laos, Vietnam, Cambodia, and Thailand. As a result, they found that, of the 188 tablet packs purchased which were labelled as “artesunate,” 53% did not contain any artesunate.⁴

Colombia's drug regulatory authority confiscated 6 million doses of counterfeit diclofenac a couple of years ago. This number far exceeded the annual consumption of the drug in Colombia, which means the fakes were manufactured for export.³

Last year in Britain, the Medicines and Healthcare products Regulatory Agency (MHRA), in conjunction with Pfizer, recalled packs of atorvastatin 20 mg tablets, and in 2004 the Royal Pharmaceutical Society found that half of all drugs for erectile dysfunction sold online were fake.⁵ Customs and Excise seized 231 151 counterfeit sildenafil (Viagra) tablets in a single year.⁵

In 2000, 5-10% of all drugs on the Russian market were found to be fake.³These statistics are just a minute representation of the extent of the drug counterfeiting problem worldwide.

But surely regulatory authorities and pharmaceutical companies would notice the problem if thousands of fraudulent copies of drugs are being sold on the market? There must be records of how many drugs are sold? Well, fake drugs are being channelled into the market through numerous routes, legal as well as illegal. Counterfeiters get away with it as jurisdiction over pharmaceutical distribution is poor, with wholesalers, distributors, pharmacies, and village shops buying, selling, and reselling through unofficial channels, often with no proof of the medicines' authenticity.¹ Moreover, pharmaceutical companies are reluctant to report sales of fraudulent copies of their drugs² for fear of negative repercussions on their products' reputations and sales records.

Health consequences

The most obvious consequences of fake drug ingestion are unnecessary and preventable disease relapse, decline in health, lack of symptom improvement, and death. In cases where the active ingredient is replaced by toxic substances, side effects, poisoning or death may occur. It is estimated that in 2001 in China, fake drugs led to the deaths of 192 000 patients who were given ineffective treatments.³

As well as being a threat to health on an individual basis, fake drugs boost the spread of infection through entire communities by increasing drug resistance. Fake drugs contribute to the rise of antibiotic resistance worldwide, rendering infections, especially hospital acquired infections, a nightmare to battle.³ Using substandard drugs—that is, where the dose of active ingredient is smaller than the minimum dose needed to treat the disease—favours the development of resistance. This is because the dose of the active ingredient is not substantial enough to kill the organism in question but is sufficient to help it develop a resistance mechanism.⁴ Conversely, the unwitting use of substandard or counterfeit medication can lead to erroneous reports on drug resistance; since in reality, effective treatment had never been given.⁶

Alarmingly, many of the areas with a high incidence of tuberculosis, malaria, or HIV are also those parts of the world suffering most from fake drugs. The incidence of tuberculosis is falling in all countries except those with a high prevalence of HIV, where it is on the increase.⁷ About one third of people infected with HIV are also infected with tuberculosis, and 70% of these people live in sub-Saharan Africa.⁸ This synergistic phenomenon, together with the emergence of multidrug resistant tuberculosis aided by abundant supplies of fake drugs, could, in theory, lead to a pandemic. In the case of malaria, we already know that up to 60% of antimalarials sold in parts of Southeast Asia are fake.³

The effects of fake drugs are not confined to enhancing antimicrobial and antiviral drug resistance. The BBC2 television programme Bad Medicine, broadcast on 12 July 2005, is an excellent source of information on the effect of the counterfeit drugs trade on individual and community health, particularly in Nigeria, and how the Nigerian National Agency for Food and Drug Administration and Control is fighting it. A shocking example was the story of a Nigerian paediatrics hospital that had been stocked up with counterfeit drugs, resulting in a devastating number of preventable deaths.

How does this affect you?

Sixty per cent of reported cases of counterfeit drugs are in the developing world,¹ with Southeast Asia harbouring some of the larger fake drug rings. Consequently, travellers heading to any part of the developing world should check WHO recommendations on drug purchase.¹

Because drug counterfeiting is a constant problem in the developing world, medical staff and students training and living in such areas are more aware of risks. Conversely, their colleagues, travelling in from developed countries, are less likely to be prepared for health threatening eventualities. For example, despite strict medical school regulations and concerns about bloodborne viruses and other infectious diseases, some elective students opt to buy prophylactic treatment on site from small pharmacies to avoid paying private prescription charges of up to $250 imposed by several medical schools.

Aggravating factors

An intricate network of factors has fuelled the counterfeiting business for centuries. With the proliferation of free trade agreements, the increment in the number of channels through which drugs are trafficked, and poor education for patients, eradicating this fraudulent trade is proving to be very difficult. In 1999, the WHO Guidelines for the Development of Measures to Combat Counterfeit Drugs identified key factors that fuel the problem (box 1).²

What can be done?

The 1999 Guidelines for the Development of Measures to Combat Counterfeit Drugs also provide a plan of action to bring the business to a halt.² These are outlined in box 2.

To date, many countries have taken successful steps towards a safer pharmaceutical market. In 2001 Italy's Ministry of Health increased its campaign against counterfeit drugs by introducing a new technology called a “quality stamp” on every package of prescription drugs. The stamp signifies that the pharmaceutical product is a valid product, and each stamp has a batch number that will allow the product to be traced.⁴ Similarly, Nigeria's National Agency For Food And Drug Administration And Control continues its efficient fight against the counterfeit drugs traffic in Nigeria, banning imports from certain manufacturers and confiscating fake drugs. Its team are experts at distinguishing between fake and real packaging, as shown in a television programme in July 2005.

Patients' involvement in combating fake drugs becomes essential as we move towards a patient centred medical practice. Therefore, campaigning for patients' education by changing the existing self-medication mentality, increasing patient compliance and raising both clinician and patient awareness on the current status of counterfeit drugs should be a priority.

Conclusion

The seriousness of the current situation in fake drugs trafficking cannot be over-emphasised; the problem is at least 2500 years old and still growing. It is a substantial cause of death in many parts of the world and a contributor to the emergence of new drug resistant strains of tuberculosis, malaria, and HIV. The West is the latest region affected by the fake drug trade epidemic, with counterfeit statins, drugs that enhance sexual function, and many others flooding the European and American markets. Maybe this will stimulate the developed world to invest time and money in countering the problem. The international community and authorities must learn from the successful action taken by certain countries and organisations to tackle the issues surrounding the fake drug trade.

1. World Health Organization Regional Office for the Western Pacific. Counterfeit medicines: some frequently asked questions 2005. www.wpro.who.int/media_centre/fact_sheets/fs_20050506.htm (accessed 21 May 2006).
2. Department of Essential Drugs and Other Medicines. Guidelines for the development of measures to combat counterfeit drugs. Geneva: World Health Organization, 1999. (WHO/EDM/QSM/99.1.)
3. Wertheimer AI, Chaney NM, Santella T. Counterfeit pharmaceuticals: current status and future projections. J Am Pharm Assoc 2003;43;710-8.
4. Dondorp AM, Newton PN, Mayxay M, Van Damme W, Smithuis FM, Yeung S, et al. Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials. Trop Med Int Health 2004;9;1241-6.
5. BBC News Online. Fake drugs find leads to recall. 2005 http://news.bbc.co.uk/1/hi/health/4725881.stm (accessed 21 May 2006).
6. Newton PN, White NJ, Rozendaal JA, Green MD. Murder by fake drugs. BMJ 2002;324(7341):800-1.
7. Elzinga G, Raviglione MC, Maher D. Scale up: meeting targets in global tuberculosis control. Lancet 2004;363:814-9.
8. Zumla A, Malon P, Henderson J, Grange JM. The impact of the human immunodeficiency virus (HIV) infection epidemic on tuberculosis. Postgrad Med J 2000;76:259-68.

   

           

	Life Bad Medicine       Jihène El Kafsi,Peter Raven (July 2006)
	Suvash Shrestha (July 9th, 2006)       Third year M.B.B.S,Kathmandu Medical college, Sinamangal suvash_sht@yahoo.com
	At the time when world is focusing all its efforts on fighting disastrous diseases like bird flu and HIV/AIDS, drug counterfeiting seems to be little cared for despite its huge effects on the whole global health. As truly depicted in the article fake drugs are no less harmful than any disease condition and with all its effects like disease relapses, treatment failure, increase in drug resistances etc. Here I would like to mention some things which have quite an impact on this topic. Doctor-pharmaceutical relation It's commonly seen that the pharmaceutical companies shower the doctors with gifts in return to which the doctors prefer prescribing their products to the products of other companies without even caring for the quality of the drugs. So, in this circumstance the fake drugs and substandard ones may easily gain access and dominance in the market. And also the pharmaceuticals may focus more on pleasing the doctors and advertising their products rather than to improve their quality. So this may reduce the quality of drugs. So, having said that, one of the ways to block the fake drugs may be to caution the doctors not to prescribe drugs which are new and which have not been well tested and which have not been approved of. Lack of education and self medication Especially in the developing countries, it's a common practice to treat oneself. They just consult their family members and friends and since majority of drugs are available over the counter, they just buy the medicine themselves. This just may be one of the reasons fake drugs has been difficult to control. Because general people usually do not even have any idea that fake drugs do exist. And they also go for cheaper ones, so there are high chances that they end up with fake drugs. Besides these, there are also a high probability of expired drugs being used because the uneducated ones do not have an idea that drugs should not be used after certain period of time and they can easily be cheated and expired drugs are no better than the fake drugs. So, educating and generating awareness at the grass root level is needed in addition to the strict rules for the control of fake drugs.