Faking It

How do you know that the medicines you are taking are the genuine article? Counterfeiting is an increasingly costly and dangerous problem in the pharma sector

Counterfeit medicines ; at best they will do you no good and at worst they could kill you. Defined by the World Health Organisation medicines that are 'deliberately and fraudulently mislabelled with respect to identity and/or source', and that 'may include products with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging', counterfeiting is a problem that affects both branded and generic products.The scale of the problem is difficult to estimate with any degree of accuracy, largely because the consequences go unnoticed in the majority of cases - although the drugs are not effective, they are not causing an adverse reaction severe enough to be noticed above the symptoms of the condition itself. However, it is likely that counterfeit drugs have killed and injured thousands around the world, according to Reconnaissance International., a global intelligence source on authentication with offices in the US and Europe, which organised the first Global Forum on Pharmaceutical AntiCounterfeiting in Geneva, Switzerland, last September.

billions lost

The Counterfeiting Intelligence Bureau estimated that even in 1991 5% of all world trade was counterfeit, and a study by the Centre for Economics and Business Research into the economic impact of counterfeits within the EU concluded that 5.8% of the pharma industry's revenue - worth €1.5bn (US$1.48bn) at 1998 prices - is lost to fakes.

Recent work carried out by Dr Paul Newton of Mahidol University, Bangkok, shows that around a third of antimalarial treatments on sale in Cambodia, Thailand and Vietnam contained no active ingredient. Similarly, Professor Robert Taylor from Robert Gordon University in Aberdeen, Scotland, found that nearly half the drug samples analysed from pharmacies in Nigeria were defective. And there is no reason to suppose that these high ratios of counterfeits are any different in most other developing countries.

Although the problem is traditionally associated with developing countries, industrialised countries are not immune. In the UK, for example, fake Zantac found to originate in Greece was discovered in pharmacies back in 1989.

More recently there has been a spate of counterfeit drugs found in the US - one of the most regulated pharmaceutical markets in the world. For example, in May 2001 Amgen, the world's largest biotech company, reported that counterfeit Neupogen containing no active ingredient was in circulation in the US. In the same month, Serono reported that it had discovered a batch of counterfeit Serostim, a growth hormone used to treat HIV/AIDS wasting. A year later, there were reported incidents of tampered Zyprexa, the psychiatric drug from Eli Lilly; relabelled vials of Amgen's Epogen; relabelled Comibivir, the anti-retroviral drug from GlaxoSmithKline; and more fake Serostim, apparently purchased off the Internet.

Bulk APIs are also targeted by counterfeiters. From 1989-1994 the FDA identified 1,974 adverse reactions (including 49 deaths) associated with the use of gentamicin. The 'vast majority' of these were linked to formulations in which the bulk ingredients were manufactured by Long March Pharmaceuticals, of Sichuan, China.

death links

A criminal investigation found that international bulk drug brokers were falsifying records, substituting product and repackaging drugs for sale to the US pharmaceutical industry. But adverse reactions to gentamicin continued to be reported, however, and in 1998/99 both Fujisawa and ESI Lederle voluntarily recalled batches made from Long March bulk APIs.

From 1 May 1999 to 11 January 2000, 254 adverse events were reported, including 17 deaths, and concern was again expressed that the contaminated gentamicin and other counterfeit products could still be entering the US either directly or through various transshipment points, including Germany and other European centres.

The number of deaths and degree of certainty linking deaths to specific APIs is still being debated. But the fact that dangerous counterfeit bulk drugs can and have entered the US healthcare system is not in dispute. One FDA investigator wrote: 'Counterfeit and unapproved bulk drugs can unknowingly be turned into tablets/capsules and can reach anyone, including the President.'

low cost dilemma

The need for access to low-cost medicines in poor countries has introduced a new dimension to the counterfeiting issue, says Reconnaissance International. It has been shown that low-cost drugs originally destined for Africa have been illegally diverted to Mexico. And from Mexico, there is a thriving movement into the US, demonstrating the ease with which counterfeits can enter one of the strictest regulatory environments in the world via the back door.

This is a dilemma that can only be resolved by world authorities, working with the drug companies, the health authorities and regulators. To date, anticounterfeiting initiatives have been driven by governmental organisations such as the FDA, NGOs, international organisations such as WHO and the WTO, by the pharmaceutical trade associations (national and regional) and by the individual efforts of the pharmaceutical companies themselves. Consumers of counterfeit medications also have a role to play by denouncing and taking legal action against counterfeiters.

There are a number of ways in which fake drugs can enter the market:

• There is an active international secondary market in bulk APIs and excipients with some criminal traders cutting/diluting the genuine product or substituting it with fake material;

• Increasing numbers of counterfeit pills, injectables, topicals and other medicines often contain no active ingredients (or even harmful material) but are packaged to look almost identical to the real thing;

• In the US and some other countries, the active secondary market in pharmaceutical goods does not require strict traceability, allowing criminals to insert counterfeits into supposedly well-controlled distribution systems;

• The expiration or tracking information on expired, reject or stolen medicines is changed and the products resold into the distribution system. Sometimes the original product is removed and fake drugs placed in the original packaging;

• There is an active shipment route of pharmaceuticals from Asia and Africa back to the US and Europe. Sometimes these shipments are mixed with counterfeits, sometimes they are stored or shipped improperly and degrade by the time they are used;

• The dramatic growth of Internet pharmacies, many with undisclosed location, uncertain prescription, dispensing and quality precautions represents a substantial opportunity for counterfeiters.

The counterfeiting problem is particularly acute in the pharmaceutical sector because of the health and safety implications, says Reconnaissance International. But there are a number of measures that can be taken to counteract the risk.

Successful anticounterfeiting measures should start from the top, with governmental policy enacted to prohibit counterfeit medicines, ensure enforcement of drug laws, tighten up protection of intellectual property and impose strict sanctions and penalties on counterfeiters. But the activities of governments, regulatory authorities and the pharmaceutical industry itself will be effective only if backed up by stringent investigation and enforcement by customs, the police and the judiciary to ensure compliance with laws, dismantling of counterfeiters' operations, seizure of assets and the imposition of stiff penalties, Reconnaissance warns.

recognising the problem

A key weapon in the fight against counterfeiting is the use of technologies on or in pharmaceutical products or their packaging that either individually or in combination provide authentication, enable the products to be tracked through the supply chain and/or prevent tampering. It is likely in the foreseeable future that in some countries companies that do not currently take adequate steps to protect their products in this way will be compelled to do so by law. However, these measures need to be supported by education of the public to recognise counterfeit products and to understand the risks they represent - a recent MORI poll in the UK revealed that 5% of those asked would knowingly buy counterfeit pharmaceuticals.

Anticounterfeiting activities carried out in isolation by individual companies tend to displace rather than eradicate the problem, and are only partially successful as a result. A number of industry sectors have achieved more effective results by joining forces and associations which lobby for increased protection, pool knowledge and resources, undertake joint investigations and set common standards for securing products through the supply chain.