Counterfeits: reducing the growing threat

The value of counterfeit drugs sold globally is estimated at more than $35 billion (€27.5 billion) and the US Center for Medicines in the Public Interest recently predicted that this figure could reach $75 billion (€58.9 billion) by 2010. A report by the International Medicinal Products Anti-Counterfeiting Taskforce (IMPACT) — created by the World Health Organization (WHO) in 2006 to mobilize awareness and action in the fight against counterfeit drugs — stated that 10–30% of medicines for sale in much of the developing world are counterfeit. For medicines purchased via the internet from sites that conceal their physical location, IMPACT estimates that up to 50% may be counterfeit.¹

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Counterfeit medicines can range from 'copycat' medicines that contain the declared active ingredient, to those with inactive preparations or random mixtures of toxic substances. All counterfeits are dangerous because their content and quality are unknown. WHO has documented thousands of cases worldwide of counterfeit medicines causing serious illnesses or death because of substandard, ineffective or toxic ingredients. The threat is particularly acute in developing countries where counterfeit treatments for lifethreatening conditions such as malaria and HIV are commonly available.

In addition to their impact on global public health, counterfeit drugs pose a serious threat to the pharmaceutical industry — both to the sales of specific products and to the reputation of the industry as a whole. With the tremendous costs and challenges of bringing new therapies to market, pharmaceutical companies cannot afford the additional threat of having a product's efficacy or safety called into question because of ineffective or dangerous counterfeits. There has been much progress within the industry to test sophisticated technologies such as radiofrequency identification (RFID) to combat counterfeiting, but widespread implementation of any technological solution is still some time away. However, there are numerous steps a company can take immediately to help prevent counterfeiting, as well as improve the detection of counterfeit products that reach the market. These efforts are essential for companies to protect patients, maintain the value of their assets, and retain public trust of the industry and its products.

Assessing the threat

Any effort to improve anticounterfeiting measures should be incorporated into a pharmaceutical company's overall risk management and pharmacovigilance efforts. While pharmacovigilance programmes have traditionally focused on quality assurance and postmarketing safety surveillance of legitimate products, counterfeit drugs pose a substantial safety threat and financial risk. The risk is especially elevated for higher value products that are in strong demand; for products that are widely distributed in markets where counterfeiting is common; and for lifestylerelated therapies that are not covered by health insurance. As part of a continuing risk assessment of its product portfolio, a pharmaceutical company needs to evaluate and understand the potential counterfeiting risk factors of every product, including its overall value to the company, the markets where it will be sold, price and expected sales volume. With that information, a company can implement an appropriate risk management strategy that focuses on the products most likely to be targeted.

Many companies are changing the focus of their pharmacovigilance programmes to a more proactive approach that emphasizes risk assessment at the earliest stages of product development and integrates a companywide 'safety culture' into every part of the development process. In the same way, an effective anticounterfeiting programme requires an integrated, crossfunctional, and systematic approach that continuously evaluates the counterfeiting risk and incorporates prevention efforts into the early stages of a drug's development and formulation. Counterfeiting awareness should be established as a corporate priority, with highlevel support and clear goals for which managers are held accountable. This effort must be maintained throughout the product life cycle to ensure counterfeiting issues are kept to a minimum.

The corporate commitment to the anticounterfeiting aspect of risk management and pharmacovigilance also requires investment in the appropriate people, governance, processes and technology needed to make the programmes succeed. Rather than being an overall cost or a liability, these investments enhance the value of the company by protecting one of its most important assets: its products.

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Controlling the threat

Efforts to control the threat of pharmaceutical counterfeiting can be divided into two major categories: prevention and detection. Prevention programmes encompass all activities that contribute to making a product harder to counterfeit, as well as efforts to maintain the security of the entire supply chain. Detection programmes incorporate activities leading to the uncovering of counterfeit products that reach the market, such as marketplace sampling and analysis of adverse events or other reports from physicians or patients.

Prevention

There are two key elements in the fight to prevent drug counterfeiting: using various technologies to make a product harder to copy and bring-to-market undetected; and implementing tighter security throughout the supply chain to ensure that drug supplies, packaging, manufacturing processes and other production components are only accessible to authorized personnel.

Technology

Anticounterfeiting technologies include:

• Authentication technologies. This approach is already in common use and involves the inclusion of authentication markers on products and/or packaging that allow distributors, healthcare providers and others involved in the pharmaceutical supply chain to ascertain that the products they receive are genuine before they reach patients. These technologies include colour-shifting inks, fluorescent material, holograms, tamperevident packaging and chemical markets. They can be either overt or covert. Authentication technology provides an important layer of protection for drug authenticity, although some counterfeiters have learned to copy markers as well as products.

• Data matrix. Another technology being used on a limited basis is the data matrix, also referred to as a 2D barcode. This technology enables additional information to be imbedded in a special barcode, such as an individual serial number for each pack or other data that aid in tracking and authentication. However, this technology requires an investment in a new type of barcode reader and standards for the coding system have not been agreed upon across the industry.

• RFID. This technology, which is still in the pilot stage for pharmaceutical products, has initiated widespread discussion. It utilizes low-power radio frequencies that can be 'read' to reveal specific information about both the product's manufacture and its electronic 'pedigree'— a record of the chain of custody of the product from the point of manufacture to the point of dispensation. While there is general agreement that RFID is a promising technology for tracking and tracing drug authenticity, it also has significant drawbacks including cost, its unknown effect on sensitive products such as biologics, data privacy and the lack of industry data standards that would be needed to support such a technology. Even if these issues can be resolved, it will be several years before RFID is ready for widespread use in the pharmaceutical industry.

All of these technologies require significant investments to be effective. A risk assessment of a company's product portfolio plays a key role in determining which technology investments are appropriate for a given therapy.

Security

Supply chain security provides a second path to help prevent counterfeiting. This path is often overlooked because it is less glamorous than the technological solutions, but it is equally important, as well as less costly. This approach is focused on the entire supply chain involved in the production and distribution of pharmaceutical products, and the integrity of the various links in that chain.

Important areas for any programme to secure the supply chain against counterfeiting include:

• Examining security procedures at any outside companies that supply chemicals or other components used in drug manufacture.

• Ensuring the integrity of the companies designing and manufacturing all packaging components.

• Reviewing security standards of companies involved in transporting, wholesaling, distributing or reselling a company's products.

• Internal security reviews, which help prevent thefts of products or packaging at manufacturing facilities, maintain the integrity of authentication technologies and protect intellectual property, such as formulations or manufacturing processes.

The combination of premanufacturing (upstream) security measures and postmanufacturing (downstream) technologies for authentication provide a well-balanced approach to prevent the counterfeiting of pharmaceutical products.

Detection

Although prevention of counterfeiting is the ideal, aggressive programmes to detect counterfeit products that reach the market are also essential, given the pervasiveness of trafficking in counterfeit drugs. The authentication technologies that are important for preventing counterfeiting also play a vital role in the detection process. These technologies allow those at the dispensing end of the supply chain — such as pharmacies and hospitals — to more easily identify authentic products and separate out questionable ones before they reach patients. Continuing advances in authentication technology that bring the technologies to individual tablets or packs should improve detection at this stage. Equally important for health professionals from the pharmaceutical companies is education about the authentication methods in place for various products so they are prepared to recognize the appropriate markers.

A proactive programme of market surveillance is also important. Based on the risk assessment for each of its products, a company should conduct anonymous purchases — both wholesale and retail — of highrisk products in highrisk markets to detect the rate and source of counterfeits in those markets. Covert authentication markers known only to the manufacturer can be used to aid detection for products where sophisticated counterfeits are more likely.

Counterfeit detection awareness should also be incorporated into a company's analysis of postmarketing adverse event reports, as well as other technical complaints the company receives about its products such as lack of efficacy. There is always the possibility that an adverse event or other complaint may be initiated by a patient taking a counterfeit drug rather than the result of issues with manufacturing or with the product itself. Data that a particular adverse event is occurring more frequently in a particular market than in the past may be evidence that a counterfeit version of the product has become available in that market.

Meeting the challenge

There are several significant challenges that must be overcome to implement and maintain a successful anticounterfeiting programme in today's pharmaceutical market. One challenge is the complexity and scope of the supply chain for the global market as products are manufactured, distributed and sold in dozens or even hundreds of countries. With the huge potential profit from counterfeit drugs, there is an equally large number of people waiting to exploit any weaknesses in the supply system or insufficient regulatory oversight in certain markets. Constant vigilance is required to maintain control of a product's integrity.

Economics also play an unmistakable role in counterfeiting. There are many parts of the world — both developed and developing — where certain drugs may be unavailable to those who want or need them because they lack the income or healthcare coverage to pay for them. This situation provides an obvious opening for those offering less expensive alternatives. While pricing is a complex issue for the pharmaceutical industry, there must be an awareness of cost when evaluating the potential counterfeiting risk of any given product.

The other economics-related challenge facing the industry in the more developed world is the availability of drugs through the internet. As WHO noted, a large percentage of pharmaceutical products ordered through the internet are counterfeit and pose a significant risk to those who may be trying to save money. This is a major education challenge for the industry, which must make clear to consumers the huge health risk (not to mention financial risk) they are taking by ordering products illegally over the internet.

Clive Brading is a Director at PAREXEL Consulting.

References

Counterfeit Medicines (World Health Organization, November 2006).