THE COUNTERFEIT MEDICINES A SILENT EPIDEMIC

Dr Safaa Bahjat, Kirkuk, Iraq

INTRODUCTION

Over the past decade, the massive public health problem of counterfeit and substandard drugs has increasingly become apparent, causing a significant morbidity and mortality and reducing the effectiveness of healthcare in the developing world. There are few accurate estimates of the scale of the problem. Published estimates of the global prevalence of counterfeit drugs range from 1% to 50%. Since the pharmaceutical industries produce billions of tablets each year, even 1% of the global production would affect millions of people. Various countries use different definitions of counterfeit drugs .One of the most widely used is that of the W.H.O. where the emphasis is on the intent to deceive.

A counterfeit drug: is one which is deliberately and fraudulently mislabeled with respect to identity, source, or both Counterfeiting can apply to both branded and generic products and counterfeit products could include products with the correct ingredients or with the wrong ingredients, with out active ingredients ,with insufficient active ingredients, or with fake packaging.

Substandard drugs are genuine drug products that do not meet quality specifications set for them. If a drug, upon laboratory testing in accordance with the specifications it claims to comply with, fails to meet the specifications, then it is classified as a substandard drug.

Counterfeit and substandard medicines have a long history. In the first century in Greece, Dioscorides first classified drugs by their therapeutic use, warned of the dangers of adulterated drugs, and advised on their detection. Herbal medicines have a long history of being adulterated; for example the use of congeners to adulterate Valaerina officinalis root, used for treating cholera and red clay to adulterate the foul smelling Ferula ass-foetida, which was hung around the neck to ward off infections. Since of the discovery of potent anti-infectives there have been periodic crises in their quality .In the 17th century, the adulteration of Peruvian Cinchona bark, the first treatment of ague (malaria), with other astringent barks and aloes (assumed huge dimensions). This adulteration was precipitated by huge demands for the bark from Europe, where malaria was still endemic. In the UK, and USA in the mid-19th century, the widespread adulteration of medicine, especially quinine, prompted the first regulation of the trade in medicines, codes of practice of pharmacists and guides on the detection of counterfeit drugs. Counterfeit drugs were first addressed at an international health meeting only 20 years ago and the World Health Assembly adopted a resolution against counterfeit and substandard pharmaceuticals in 1988.

Numerous factors encourage counterfeiting drugs, apart from criminal greed. The relatively high cost of genuine medicines together with their desirability and shortage, gives the counterfeiters an economic incentive, facilitated by lack of legislation and enforcement and light penalties. There is often inadequate liaison between police, customs, and drug regulatory authorities. Lack of knowledge of counterfeits, and appropriate preventive measures, together with poor dissemination of information among health workers and the public, make their detection difficult. In the tropics many patients obtain medicines from untrained vendors without prescription, in inadequate courses, and without information. The lack of financial and human resources available to many drug regulatory authorities often makes effective recognition of poor quality drugs and actions impossible. Only 20% of WHO member states have well developed drug regulations and 30% have either no drug regulation or a capacity that hardly functions. Corruption is also an integral factor difficult to police, especially when the authorities are involved; for example, the staff of one drug regulatory authority were found to have taken bribes to pass spurious drugs for sale and drug inspectors were reported to charge wholesalers US$65 per month to allow their illegal businesses to continue. Complex trade arrangements, without proper documentation, facilitate trade in counterfeits across porous borders, resulting in a low risk, high profit venture for counterfeiters.

The consequences of counterfeit and substandard anti-infectives:

Morbidity and mortality
If medicines containing little or no active ingredients whether counterfeit or substandard are used for the treatment of common diseases with a high untreated mortality - e.g. falciparum malaria, pneuomonia, meningitis, typhoid and tuberculosis, then morbidity and mortality must increase.

Adverse effects
Counterfeit and substandard medicines could also cause adverse effects through excessive dose, or due to the presence of potentially toxic ingredients or pathogen contaminants. Although such catastrophic results as the childhood deaths associated with the consumption of paracetamol syrup have not been reported for anti-infectives, potentially dangerous unexpected pharmaceuticals have been found in counterfeits, for example, counterfeit halofantrine syrup contains a sulphonamide and some counterfeit artesunate contains aremisinin, chloramphenicol, erythromycin, paracetamol, metronidazole and metamizole. Patients could be allergic to these drugs, or might experience adverse effects, which would be clinically very confusing, since the physicians would be unaware of the true active ingredients. The substitution of aspirin for chloroquine could contribute to acidosis in children presenting with severe malaria. Pathogens have been found in liquid formulations; substandard gentamicin eye drops in Mauritius were contaminated with gentamicin-resistant Pseudomonous aeruginosa and led to severe eye infections.

Economics
The financial consequences of counterfeit medicines for the companies producing the genuine product can be enormous. It has been estimated that the fake medicines market is worth some US$35-44 billion per year. Money is lost because the health care system, patients and their families must bear the costs of increased suffering and sometimes death. Spurious apparent resistance and unusual toxicities compound the public- health toll.

Loss of confidence
Loss of faith in genuine medicines is inevitable in areas where drug quality is perceived as being poor and results in a loss of confidence in the health care system and the drug regulatory authorities if action is inadequate. Health practitioners then also lose confidence in the medications that they rely upon.

Drug resistance
Anti-infective medicines that contain sub-therapeutic amounts of the active ingredients increase the risk of selecting and spreading of resistance. For diseases that are treated with combination therapy e.g. falciparum malaria, tuberculosis and HIV -poor quality drugs risk the spread of resistance due to both the poor quality and the "unprotected" co-drugs.

Chemical characterization of counterfeit medicines

Content and dissolution properties
The ability to investigate the contents of counterfeit or substandard pharmaceuticals is a critical component of monitoring of the drug supply by drug regulatory authorities. Chemical analysis methods such as high performance liquid chromatography (HPLC) and gas chromatography coupled with optical, electrochemical or mass spectrometric detectors have been the mainstays of the pharmaceutical analysis.

Inexpensive rapid tests

The quickest and cheapest way to detect counterfeit drug is to compare the printing, embossing, shape, odour, taste, and consistency of a suspected sample with the genuine product. In the 1840s, tablets were often adulterated with clay in Europe and the USA. An ingenious rapid test used, was to place the medicine on a shovel in a fire. Only 2% dry matter was left of the genuine tablet whereas the fake left 29% dry matter. Thin -layer chromatography (TLC) is a specific, sensitive and inexpensive technique.
Colourimetry identifies particular ingredients by making use of colour changes produced by chemical reactions or complexions between the active ingredients and a specific reagent. Quantitative measurements of active ingredient concentration as a function of colour intensity can then be made with a simple handheld photometer. Characteristic physical, chemical, and chemical properties e.g. weight, density, refractive index viscosity, osmolarity, PH, crystal morphology and solubility-can be also used to identify counterfeits. Microbiological technologies have also been used. For example, an antimicrobial activity assay of different ofloxacin preparations in Pakistan against three ofloxacin- sensitive reference bacterial species, showed that three injectable and one tablet brand had reduced or no antimicrobial activity.

Interventions:

• There is clearly no single solution to the problem of counterfeit medicines, but much more can be done now to control this enormous yet neglected problem that affects particularly the poorest, most vulnerable people.
• Urgent support is needed for the 30% of the world's countries that have no drug regulation or a capacity that hardly functions.
• Good quality anti-infective medicines, with distinctive markers of quality assurance, should be readily available and inexpensive or free, to undercut the counterfeiters.
  
• It should become a legal requirement to report any substandard or counterfeit drugs to the respective national drug regulatory authority, which in turn should report to the WHO. WHO should develop a centralized database that drug regulatory authorities and medical practitioners can consult for local current detailed information.
  
• Monitoring for counterfeit rugs and substandard medicines should be an intrinsic part of disease surveillance programs.
  
• Severe penalties commensurate with the severity of the crime are required for those who knowingly manufacture counterfeit medicines. Police and custom authorities should be mandated to regard counterfeit medicines with the same gravity accorded to narcotic production and distribution.
  

REFERENCES

Paul N Newton ,Micheal D Green,Facundo M Fernandez,Nicholas PJ Day,Nicholas J White. Counterfeit anti-infective drugs The Lancet Infectious Diseases 2006;6:602-613.