Substandard medicines: a neglected epidemic of poverty

by Paul Chinnock, TropIKA.net:

It is very unlikely that the people responsible for making the teething mixture that caused the deaths of at least 34 children in Nigeria last year actually wanted to kill the victims of their inept efforts to produce a paracetamol syrup. Nevertheless, they used toxic diethylene glycol (DEG) as a solvent, instead of propylene glycol, with appalling consequences.

All of us are taking more medicines. We hope that they will be of benefit, not harm, to our health. But the expanding drugs market offers opportunities both for the mainstream pharmaceutical industry and for those who produce substandard medicines. An increasing number of the drugs in circulation are substandard. While there are some concerns over such drugs in the developed world, it is the poorest people in the poorest countries who are most likely to suffer the consequences. In some of these countries the proportion of drugs in circulation that are substandard exceeds 30%.

Medicines for the treatment of infectious diseases are amongst those most often encountered in substandard versions. Fake antibiotics are commonplace in many countries. The development of resistance to antimalarials and antituberculosis drugs has been aided by substandard drugs, which often contain small, inadequate doses of the active ingredient.

The past few weeks have seen a number of articles appearing in the medical journals discussing the continuing rise of counterfeit and substandard medicines.

Data lacking

In a Clinical Pharmacology & Therapeutics article (1), Andreas Seiter of the World Bank's Health, Nutrition and Population division draws attention to the lack of reliable data on the prevalence of substandard drugs. Nevertheless, he estimates that 800,000 fake malaria treatments are given each year, around half of them to children, resulting in "several thousand additional deaths". The uncertainty as to the scale of the problem makes it hard to for policy makers to decide what proportion of the scarce resources available for global health should be devoted to the issue.

Seiter does not neglect the economic burden, noting that four working days are typically required to pay for each worthless malaria treatment. He continues: "Most of this economic burden would need to be shouldered by the poor, who are also more likely to buy counterfeit and substandard drugs from informal sellers that escape government regulation."

The drug industry is damaged by counterfeiting, but companies bring to the attention of authorities mainly those cases that affect their leading brands. As Seiter notes, "... the loss of human lives and leakage of cash out of poor people's pockets occur elsewhere without anyone taking notice".

Seiter also points out that, "International experts are debating whether it makes sense to differentiate between deliberate counterfeiting and neglect of quality standards in manufacturing". Another instance of the inclusion of DEG in paracetamol syrup, which led to 200 deaths in Paraguay, involved a product made in a government manufacturing plant.

The erosion of public trust in health-care providers is another consequence of the increase in ineffective drugs in circulation.

Seiter concludes that the solutions required will vary between countries, cautioning against a one-size-fits-all approach.

Children at risk

A short ‘Perspective' article in the Archives of Disease in Childhood (2) argues that it is the children of the poor who are most vulnerable to fake or substandard drugs. Mario Bonati of the Laboratory for Mother and Child Health at the Mario Negri

Pharmacological Research Institute in Italy points out that a high proportion of treatments for many conditions are given to children. Should a child in a low-income country be harmed by a substandard drug, as in the case of the DEG poisonings, difficulties in diagnosing and treating the resulting condition reduce the chance of recovery.

Technology

A view from the South comes in an article in the East African Journal of Public Health (3) by Dr E. D. Nsimba, of Tanzania's Muhimbili University. He discusses the range of issues around substandard drugs but his main conclusion is that "Developing countries should try their best at all costs establish good laboratories for monitoring or checking for quality control for all pharmaceuticals locally manufactured and those imported (entering) or donated to countries to make sure that they meet the set or established international or national standards". He says that new technologies now becoming available will make it easier to maintain quality in the supply chain.

Interestingly another recent article, not in a medical journal but in the New York Times (4), discusses some of these new technologies. Facundo Fernández, a chemistry professor at the Georgia Institute of Technology is using techniques developed to detect cocaine smugglers to find ways of identifying fake medicines. He says, "I always dream that at some point the end-consumer will be able to check. You put your tablet in front of a machine and you get a red light or a green light. That would be the end of counterfeit drugs." But new technologies are expensive and it is hard to imagine end-consumers in Africa having access to machines like those of Professor Fernández any time soon. (Fernández is also investigating the possibility of using mass spectroscopy to test whether insecticide-treated bednets are genuine.)

As the NYT article also discusses, technology can be employed by the authorities to help trace the source of counterfeit products. The use of pollen markers made it possible to trace several fake drugs back to their origin in China, and research still in progress at the Centre for Tropical Medicine in Laos, is seeking to determine whether counterfeit antimalarial drugs found in Africa were imported from Asia or manufactured locally.

Uganda's dilemma

A Lancet article (5) focuses on the dilemma faced by policy makers in Uganda, where there have been calls for a proposed anti-counterfeiting bill to be redrafted, as in its present form critics believe it could lead to the prosecution of importers of generic medicines which contain genuine drugs but nevertheless infringe patents.

The article also highlights the fact that there are differences of opinion globally on how to handle the issue. Some authorities argue that counterfeits and products that infringe patents are separate problems but not everyone in the drug industry is happy with this approach. The article also describe the position adopted by Médecins Sans Frontières, which believes that the present counterfeiting agenda has skewed attention towards chasing criminals, when substandard drugs produced by legitimate manufacturers pose a much greater public health problem. The priority, according to MSF, should be to boost weak drug regulators, and provide the resources to help them routinely track down and test the quality and safety of drugs.

"A long and complex path"

An article in Research in Social and Administrative Pharmacy (6) again stresses the seriousness of the situation, which it describes as "a macroeconomic pandemic". It also notes that estimates of the costs of fakes, to health and to the economy, remain "sketchy". The authors remind us that vaccines as well as drugs can be counterfeited: "During a meningitis epidemic in Niger in 1995, over 50,000 people were inoculated with fake vaccine, resulting in 2000 deaths".

When people cannot access or cannot afford to buy through legitimate channels, the article points out, they will turn to other unregulated sources, where there is a high likelihood that the products they find will be substandard or fake. Shortages of supplies of genuine drugs encourage the proliferation of fakes. Addressing the problem of ‘stock-outs' must therefore be a part of the solution.

This is a comprehensive article that is worthy of study. It includes a discussion of potential anti-counterfeiting strategies. Noting that "The path of a counterfeit or substandard medicine is normally long and complex," the authors discuss measures that can be taken at the stages of manufacturing, shipping, finance and distribution. Unusually, for a discussion on this issue, the article states frankly that corruption within regulation systems is a major factor that allows the fake drugs problem to continue; it calls for "Harsh penalties and example setting when corrupt practices have been discovered".

As all of these articles show, the pandemic of substandard drugs is now causing widespread concern. Certainly there is no shortage of opinion and expressions of outrage. But there is still a lack of data and a lack of action. Just as the infectious diseases of poverty themselves continue to be neglected, the threat posed by substandard products to efforts to improve their control is not receiving an adequate level of attention from the global community.

IMPACT

For more information on substandard drugs and the efforts being made to control the problem see the website of IMPACT - the International Medical Products Anti-Counterfeiting Taskforce. IMPACT was launched in 2006 by the World Health Organization, which defines counterfeits as follows:

"Counterfeit medicines are deliberately and fraudulently mislabelled with respect to identity or source: their quality is unpredictable as they may contain the wrong amount of active ingredients, wrong ingredients or no active ingredients."

References

1. Seiter A (2009). Health and economic consequences of counterfeit drugs. Clin Pharmacol Ther; 85:576-578. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19451909

2. Bonati M (2009). Once again, children are the main victims of fake drugs. Arch Dis Child; 94:468. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19460926

3. Nsimba SE (2008). Problems associated with substandard and counterfeit drugs in developing countries: a review article on global implications of counterfeit drugs in the era of antiretroviral (ARVs) drugs in a free market economy. East Afr J Public Health; 5:205-210. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19374325

4. Fuller T (2009). Using Scientific Tools in an International War on Fake Drugs. New York Times. Available on line: https://www.nytimes.com/2009/07/21/science/21coun.html?hp&_r=0. Accessed 31st July 2009.

5. Anderson T (2009). Confusion over counterfeit drugs in Uganda. Lancet; 373(9681):2097-2098. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19551913

6. Wertheimer AI, Norris J (2009). Safeguarding against substandard/counterfeit drugs: mitigating a macroeconomic pandemic. Res Social Adm Pharm; 5:4-16.Available from: https://www.ncbi.nlm.nih.gov/pubmed/19285285