The Growing Threat of Counterfeit Drugs

The deaths in January of more than 100 Pakistani heart patients, as well as the ongoing treatment of 300 more, at the Punjab Institute of Cardiology hospital underscores the seriousness of the counterfeit drug crisis across the globe. Similar to many other counterfeit drug incidents that have been growing at an alarming rate, these patients were prescribed substandard medicine. What’s atypical and even more unsettling about this incident, however, is that the medicines, one of which was contaminated and all of which contained the toxic ingredient pyrimethamine (used for the treatment of malaria), are known to have been manufactured by three pharmaceutical companies. One company’s license had long expired, yet it continued to manufacture the contaminated drugs in bulk and supply them to government hospitals and open markets.¹

According to the U.S. Food and Drug Administration (FDA), the number of counterfeit drug investigations has grown almost tenfold in the last five years.² An ABC news report in February reported that the FDA recently shut down a number of websites that purported to sell drugs for heart disease, epilepsy and anxiety. They listed for sale more than 40 prescription drugs, including Depakote, Zoloft, Lipitor and Xanax — all of which turned out to be fakes. “A lot of these drugs are ordered over the Internet from what appear to be legitimate pharmacies and are shipped directly to the patients by the counterfeiters,” said the U.S. Customs and Border Protection’s Therese Randazzo.³

The FDA estimates that less than 1 percent of drugs on the U.S. market are counterfeit; however, that is still as much as a one-in-100 chance of obtaining an illicit product. In addition, of the four billion prescriptions filled in the U.S. each year, as many as 40 million may be filled with counterfeits.²

Counterfeit Drugs Defined

“Counterfeit,” “fake,” “substandard” and “gray” are words often used interchangeably to refer to counterfeit medicines. Yet, each of these words has a specific definition. Known as spurious/falsely-labeled/falsified/counterfeit (SFFC) medicines, the World Health Organization (WHO) defines counterfeit, or fake, drugs as those that are “deliberately and fraudulently mislabeled with respect to identity or source.” Substandard drugs are defined as “genuine drug products which do not meet quality specifications set for them.” However, if substandard drugs are knowingly produced to make an unlawful product, they too are considered counterfeit. And, the gray pharmaceutical market is defined as one in which illicit profiteers are outwardly marketing competitive brands without regular approval. While gray pharmaceuticals are rarely counterfeit, per se, they are often substandard, and they have all of the negative consequences of a counterfeit drug, including circumventing health regulations, undercutting public confidence and providing an easy source of income for criminals.²

All kinds of medicines are counterfeited — both branded and generic. According to Margaret A. Hamburg, MD, FDA commissioner of food and drugs: “They may contain too much, too little or the wrong active ingredient, and they could contain toxic ingredients. They also can increase the likelihood of drug resistance, and they may prevent patients from getting the real medical products that they need to alleviate suffering and save lives.⁴ Indeed, according to the ABC news report, a series of raids all over the world have uncovered counterfeit pill-making operations. In Ecuador, boric acid, used to kill cockroaches, was one of the ingredients going into pills. In Montreal, counterfeiters used lead-based wall paint to give pills the well-known blue color used in real Viagra. In Colombia, drugs were made using Sheetrock and rat poison. In Hungary, investigators found pills that contained speed.³

The most popular medicines targeted by counterfeiters are those used to treat chronic conditions. These range from hypertensive drugs to diabetes medicines. In fact, the more expensive the drug, the more profitable the margins for counterfeiters because these medicines often consume a significant proportion of individual or family income, so chronically ill people seek places to purchase at a cheaper cost.⁵

Antibiotics, corticosteroids, erectile dysfunction drugs, cancer drugs and antiretrovirals for HIV/AIDS also are among those most counterfeited. In terms of number of incidents, the top therapeutic areas for counterfeits are cardiovascular, central nervous system, cytostatic, anti-infective, musculoskeletal and alimentary, according to Pharmaceutical Security Institute (PSI) Chief Executive Thomas Kubic.⁶

The latest criminal trend is the importation, repackaging and sale of difficult-to-counterfeit drugs, including biological formulations. Biologics are particularly difficult to detect because they are typically administered through injections and, therefore, cannot be discerned by taste. An example of this occurred in November 2009 when illegally imported human immunoglobulin (IG) vials from a company in Mumbai were seized. Because the product contained IG, it appeared that the vials were imported from a lesser producer in China and repackaged under a leading brand name. And, they were being offered at 25 percent less than the market price.²

A Growing Public Health Risk

Worldwide, the massive increase in counterfeit drug sales has risen to more than $75 billion, an increase of more than 90 percent from 2005.² It is now thought that the counterfeiting trade has become more lucrative than the narcotics business.⁶ According to WHO, in some countries around the world, counterfeit prescription drugs comprise as much as 70 percent of the drug supply, and they have been responsible for thousands of deaths in some of the world’s most impoverished nations. Peter Pitts, president of the Center for Medicine in the Public Interest and former FDA associate commissioner, estimates that counterfeit drugs may grow by 20 percent annually in coming years. And, if this estimate is correct, the counterfeit pharmaceutical industry could generate as much cash as the world’s fourth-largest healthcare company, AmerisourceBergen,with revenues of approximately $79 billion in 2011.⁷

The results of this can be tragic. In her speech at the Partnership for Safe Medicines Interchange 2010 in October 2010, Dr. Hamburg recounted many incidents over the past several years, including:⁴

• In Haiti, Panama and Nigeria, many children died due to cough syrup and teething medication poisoned with diethylene glycol.
• In 2008, adulterated heparin caused injury and some deaths in patients throughout the world.
• In early 2010, patients received counterfeit over-the-counter diet pills that had an ingredient that is found in a prescription diet pill, causing great risk for patients with cardiac conditions.
• In the summer of 2010, the FDA found that patients were using insulin from the same lot numbers stolen months before — insulin believed to have been stored or handled improperly, thereby compromising its potency.

Infiltrating the Supply Chain

Counterfeiting stems from a variety of factors, including an increased number of imported drugs, theft, growing sophistication among counterfeiters and lack of regulatory oversight. “Today, nearly 40 percent of the drugs Americans take are imported, and nearly 80 percent of the active ingredients in the drugs on the American market come from overseas sources,” explains Dr. Hamburg. “As a result, the supply chain — from raw material to finished product — has become more complex and mysterious, involving a web of repackagers and distributors in a variety of locations.” This proliferation, she adds, can infiltrate the drug supply.⁴ Add to this the growing size and sophistication of counterfeit rings, as well as increased involvement of organized transnational criminals and even international terrorist groups, including the Russian mafia, Colombian drug cartels, Chinese triads, Mexican drug gangs and even Hezbollah and al Qaeda, who are finding counterfeiting pharmaceuticals an appealing source of illicit revenue since the legal implications are routinely much lower in comparison to illicit narcotics trafficking.²

While counterfeiting occurs all over the world, the United Nations Office for Drugs and Crime reports that it occurs more often where regulatory capacity is low. For instance, surveys of anti-infective medications in Asia and Africa have found as much as 60 percent of local drug supplies with active ingredients outside of medicinal limits. In fact, a recent WHO study found that less than 20 percent of the organization’s member states are thought to have a well-developed drug regulation system. This lack of regulatory mechanisms makes it easy for counterfeiters to access legitimate channels of distribution.

And, once drugs are on the market, there is even less oversight in most areas of the world. This is because far more effort by drug regulatory systems in most countries is spent on premarketing approvals rather than on post-market monitoring.²

Detecting a Fake

Because the burden of detection and reporting lies primarily with the pharmaceutical companies, most have taken steps to mark their medications so they can be identified against counterfeit versions. Some of the methods used to differentiate genuine medications include holograms, embossing, special ink and two-dimensional bar codes. However, many of these methods have proved to be easily copied by counterfeiters, such as invisible ink, which can be easily reproduced with any standard printer. And, some of these methods require special training to read the marking and to be able to tell a genuine from a fake. To overcome this, MPedigree launched a program that allows codes from medications to be sent through a text message for free. The program then checks whether or not the medication is genuine and notifies the requester. In addition, one of the latest methods is Cryptoglyph, which places an invisible dot pattern over an entire package or label that is impossible to erase or duplicate.⁸

Unfortunately, physicians and consumers can still easily be fooled by a counterfeit medication. One reason it is so difficult to detect counterfeit medicines is that they appear strikingly similar to the genuine products. But, there are ways to detect counterfeit drugs. Packaging that is unsealed, labels that are changed or anything that is open inside an outer package should be looked for. The batch number on the outside of the package should match the number on the inside of the package. In addition, packaging should be compared with other packaging for the same drug. While the packaging may look identical, upon close inspection, there may be a different color on the logo or design on the box. The appearance of the drug also should match; if it looks different, it could be counterfeit. And beware of price. Anything dramatically cheaper could be counterfeit. Last, physicians should be cautious about a drug if patients report not feeling right or that the medication isn’t working.⁹

Measures to Stymie Trafficking

According to Dr. Hamburg, the FDA has taken a number of significant steps since the heparin contamination crisis in 2008 to prevent similar situations from occurring. It has developed “risk models to help identify drug ingredients at risk of economically motivated adulteration so it can target its efforts.” It also has developed “standards for track and trace systems that enable the identification of these products and facilitate efforts to recall them.” It has established “overseas posts in China, India, Europe and Latin America, and it is currently doing so in the Middle East.” It has established a “standard for unique identifiers for packages of drugs that creates a ‘license plate’ for individual packages of drug products as they travel through the supply chain.” And, it has established a new “Drug Integrity and Security Program based in the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, which will focus on issues such as counterfeiting, economically motivated adulteration, diversion, cargo theft and other supply chain threats.⁴

Bills were introduced both in the House and the Senate in 2011 to increase the penalties for trafficking in counterfeit drugs. Both versions of the proposed Counterfeit Drug Penalty Enhancement Act of 2011 (H.R. 3468 and S. 1886) would amend the law that criminalizes the use of counterfeit marks on or in connection with goods or services and would increase the maximum punishment for an individual counterfeiter from five years to 20 years in prison. The Senate approved the bill in a unanimous voice vote on March 6, and as of this writing, the legislation heads to the House. And, a similar measure was introduced in October as part of H.R. 3261, the Stop Online Piracy Act (or SOPA bill), aimed primarily at shutting down websites that traffic in goods that infringe on copyright or trademark rights. The SOPA provision would clarify that the counterfeit law applies to drugs, but it would only enhance the penalties in cases involving serious bodily harm, death or counterfeit military goods or services.¹⁰

A Worldwide Problem

Counterfeit drug trafficking is an extremely dangerous problem that impacts both developed and undeveloped nations. Many organizations are implementing procedures to detect these counterfeits, and government is pushing to enact laws to punish those who are profiting from this crime. However, in the end, it will take the cooperation of all countries working together to solve this growing threat to global public health.