Body + Brain

20
Aug

Cracking Down on Counterfeit Drugs

People who saw Rick Hitsman in court say he looks like any other middle-aged man with gray hair and blue eyes. For years, until he was indicted in 2012, Hitsman travelled back and forth between Arizona and California, selling counterfeit Viagra out of the trunk of his gold Toyota Camry. He’d meet buyers at parking lots around the San Fernando Valley and sell them boxes of fake Viagra, each containing four tablets, for $10 per box. Real Viagra costs around $22 per pill, so for buyers it was quite a bargain. Hitsman also sold fake Viagra online, advertising on Craigslist. Unfortunately for him, one of his customers was a man named “Mike,” a private investigator working for Pfizer.

For two years, “Mike” bought counterfeit Viagra from Hitsman and sent samples to Amy Callanan, a senior scientist at Pfizer. Callanan, who works at Pfizer’s R&D campus in Groton, Connecticut, is now sitting with me at a large conference table scattered with baggies, blister packs, and bottles of pills. Callanan spends most of her time analyzing fake pharmaceuticals, looking for chemical clues that may lead investigators to culprits. She picks up two small cardboard boxes. One box contains legitimate Viagra, the other is full of fakes. To me, they look almost identical: same size, same wide blue stripes down the left-hand side, legitimate-looking Pfizer logos and holograms.

lipitor pills
Lipitor, a statin used to control cholesterol, is among Pfizer's drugs that is counterfeited. Above, counterfeit pills (left) sit next to genuine examples (right).

But to Callanan, the fake is obvious. “I see this one all the time,” she says, handing me one of the boxes. It’s the same type Hitsman sold. “This is the most common counterfeit Viagra we see—it’s manufactured for the Malaysian market.” She points out the telltale signs of the fake: the blue stripe is too dark, the word “contains” is spelled incorrectly (“contaihs”), and the box sports a hologram that Pfizer no longer uses. But the giveaway is the lot number: 314833021, which Callanan rattles off from memory. Once a lot has been distributed to patients, Pfizer permanently retires its number. But thanks to counterfeiters, this lot number still lives on in knockoffs. It’s proven so popular among criminals that Callanan now sees knockoffs of the knockoffs. “It’s interesting how these same mistakes get perpetuated,” she says.

Fueled by easy internet sales, global supply routes, and minimal punishments, counterfeit prescription drugs have become an exploding industry, with an estimated market worth $75 billion a year worldwide. Long the scourge of developing countries, fake drugs are now popping up in the United States. In 2012, a counterfeit version of the cancer drug Avastin was widely distributed in the U.S., and a fake version of the ADHD drug Adderall, in high demand because of a shortage, arrived in the U.S. through internet pharmacies. In early 2013, the U.S. Food and Drug Administration (FDA) warned doctors that a fake version of another cancer drug, Altuzan, containing no active ingredient, was being distributed in the United States. An estimated 80% of counterfeit drugs come from overseas, and most of them are manufactured in India and China. In this era of globalization, the supply chain for genuine pharmaceuticals has grown longer, and every link offers an opportunity for counterfeiters.

A Developing Problem

In the developing world, where few countries have the regulatory and policing power of the United States, the problem of counterfeit drugs is even more widespread and tragic. For example, according to the World Health Organization, 200,000 people a year die because ineffective, fake, and substandard malaria drugs don’t clear their systems of the parasite. And because these pills often contain small amounts of active ingredient—enough to abate some symptoms but not cure disease—they contribute to drug-resistant strains. The WHO also estimates that between 1% and 10% of drugs sold around the world are counterfeits, up to as many as 50% in some countries.

In North America, the problem has been mostly—though not entirely—restricted to “lifestyle” rather than life-saving drugs. Among these, the most famous is Pfizer’s Viagra, widely described as one of the most counterfeited drugs in the world. While it’s tempting to smirk at consumers duped by fake diet pills, baldness cures, and counterfeit Viagra, these drugs are stepping stones for counterfeiters. Criminals who find success here, experts say, will likely expand their business.

China counterfeit drug manufacturing
This counterfeit drug manufacturing site in China produced fake Viagra and other drugs that were sold to customers in the European Union and the U.S.

“The ultimate way of making money, if you’re a counterfeiter, is to get into the legal supply chain,” said Roger Bate, a resident scholar at the American Enterprise Institute and an expert on counterfeit prescription drugs. “Even in the rich countries, the legitimate supply chain has been breached by counterfeiters. You could go into a CVS or a Walgreens to fill your prescription for whatever it may be—it could be for a heart medication, a cancer drug, an antibiotic—and you could be killed by that medicine.”

Pfizer won’t say how much money they lose on fake Viagra, but the drug is one of the company’s blockbusters, pulling in more than $2 billion in 2012. Viagra isn’t Pfizer’s only counterfeit headache: in 2008, according to John Clark, vice president of global security for the company, about 20 different Pfizer medicines and products were being counterfeited around the world. Today, that number is up to 60—everything from Lipitor and Centrum Vitamins to, bizarrely, ChapStick.

Pakistan Corex
Counterfeit cough syrup being dispensed from a water cooler in Pakistan.

Like Pfizer, many large companies police their brands; after all, criminals fake everything from perfume to tires. But according to Bate, pharmaceutical companies take their policing a step further. The prescription drug market is vast and lucrative—$800 or $900 billion worldwide—and counterfeiting drugs is relatively simple. “It’s probably easier to make fake pills than it is to make fake jeans, yet the markups are far greater,” Bate says. “If you are a smaller criminal getting into the fake drug business, it’s good and easy money.” It’s good money for big-time criminals as well. According to a report from the Stimson Center, a nonprofit global security institute, the Russian mafia, Colombian drug cartels, Mexican drug gangs, Hezbollah, and al Qaeda are all producing and trafficking counterfeit drugs.

The U.S. government, naturally, has laws against counterfeiting drugs, but the responsibility for enforcement is scattered across many agencies, including the FBI, the FDA, the Drug Enforcement Administration (DEA), Immigration and Customs Enforcement (ICE), and state and local police. “The FBI can look at it as a healthcare fraud case, a straight-up fraud case, or an importations case. They have the broadest reach,” says Brian Donnelly, who was an FBI agent for 21 years before becoming director of investigations for Pfizer North America. “But since 9/11—I can speak from personal experience—they’ve been sort of sidetracked onto terrorism.”

Donnelly describes his role at Pfizer as providing law enforcement with “grounders,” or cases that Pfizer has already investigated and prepped for prosecution. Pfizer’s investigative powers are surprisingly broad. After their computer experts sweep the internet for possible counterfeits, the company hires private investigators to purchase drugs from stores or online pharmacies and record conversations with sellers in jurisdictions where it’s legal. Then scientists analyze the fake drugs in one of Pfizer’s three testing facilities: Groton, Connecticut; Sandwich, England; or Dalian, China. Donnelly says his team gives U.S. and Canadian law enforcement two or three cases each week, and Pfizer’s work leads to about 50 or 60 convictions each year.

Fingerprinting the Fakes

The case involving Rick Hitsman, the man who sold fake Viagra out of the trunk of his Camry, was fairly typical. After Pfizer organized the case against him, they turned it over to ICE, who continued the investigation. Hitsman assured undercover ICE agents that the Viagra was high quality. In fact, he said, he used the counterfeit Viagra himself. He had a 28-year-old girlfriend, and the stuff would last a week. Both Callanan and Donnelly testified at Hitsman’s trial, and he was convicted of trafficking in counterfeit goods in June 2013. “It wasn’t that hard to convince the jury,” Donnelly says.

The prosecution, of course, had science on their side. In the lab at Pfizer, Callanan picks up a yellow envelope and removes an evidence bag from the Hitsman case. She opens it and pulls out a box of the infamous Malaysian counterfeit Viagra. To test the drug, Callanan scratches off a patch of blue coating, then scrapes out some of the white interior. She places the white dust into an infrared spectrometer, which shines infrared light on the sample to analyze its chemical bonds. What results is a graph of peaks and valleys—reflected and absorbed wavelengths—unique to that drug. Callanan taps the keyboard and the IR spectra from four samples from the Hitsman case appear on the screen. She zooms into the “fingerprint” region, an area of peaks and valleys that reveal secrets about the pills’ chemical makeup.

Pakistan Viagra
Counterfeit Viagra pills (left), such as these from Pakistan, may look indistinguishable from the real thing (right), but chemical analysis can reveal the fake.

“They’re all pretty similar,” she says, peering at the four red squiggles. “It looks like the same maker, but maybe different batches.” She taps on the keyboard again, and the chemical signature of authentic Viagra, outlined in black, pops onto the screen. Moving the mouse, she superimposes the real Viagra fingerprint over the fakes. “Here’s the telltale difference,” she says, pointing to a low red peak juxtaposed with a high black peak at 1700 cm -1. “This is the active ingredient—sildenafil citrate—you can see where it’s supposed to be, and how low it is in the counterfeit.”

Callanan grinds a bit more of the counterfeit pill with a mortar and pestle, and tests it with X-ray diffraction to confirm the first set of results. Here, Callanan further refines the fake’s formula by comparing it to Pfizer’s library of excipients—the inert ingredients that give a drug its form and consistency. “You see these other red mystery peaks,” she says, pointing at the screen. “Those are calcium sulfate diehydrate and calcium sulfate hemihydrate, the two most common ingredients we see in counterfeits.” Noticing my blank expression, she adds, “It’s gypsum, the same stuff as sheetrock.”

These used vials, seized during a raid in Colombia, were being washed for reuse to hold counterfeit medications.

According to Callanan, counterfeiters often add gypsum because it’s cheap, easily available, and will compress and hold the shape of a tablet. But extra ingredients like caffeine baffle her. Counterfeiters, it seems, have no limit to their imaginations. “What I really like is counterfeit Xanax spiked with melatonin,” she says with a laugh. “It’s like, why?”

“We can’t always figure out why,” adds Brian Donnelly, who is standing nearby. “But I can guarantee it has something to do with making money.”

Finding Fakes for Less

Pfizer doesn’t police the market beyond their own brands, but the company has given developing countries sophisticated handheld scanners that can detect a variety of counterfeits, including some non-Pfizer medications. But still, the largest percentage of counterfeit drugs—the generic antibiotics, tuberculosis drugs, and malaria medicines so prevalent in the developing world—often go unmonitored, since many countries don’t even have their equivalent of the FDA. For these reasons, a handful scientists and engineers are trying to create cheap, nearly indestructible devices to test for counterfeits. They want to do what Pfizer does for pennies.

One of these scientists is Marya Lieberman, a chemist at the University of Notre Dame. “In a developing country, if you go to one of the little shops that sell medications, you cannot look inside the pill and see if it’s good or not,” Lieberman says. “The technological tools that you need for that are very rare and expensive.”

To address that problem, Lieberman has developed a simple paper card that tests whether a drug contains the correct active ingredients. The user scrapes a tablet across the test card, then dips the card into water. Water travels up the card, mixing chemicals with the drug, and a colored bar code shows whether the correct ingredients are present. Lieberman’s cards currently sense 12 substances, including different types of antibiotics and anti-tuberculosis medications, as well as fillers like chalk, flour, and acetaminophen, a common additive since it lowers fevers, making patients believe the medicine is authentic. She’s currently testing the card with pharmacists in Kenya.

Right now, Lieberman’s cards only detect if an ingredient is present or absent. Her next step is to design cards that detect if the drug contains some, but not enough, active ingredient. She also wants to make the cards cheaper—they now cost about 45 cents—and easier to read.

Lieberman knows that her cards alone can’t fix the problem. Developing countries need trustworthy agencies to regulate and distribute drugs. Governments need stiffer penalties for counterfeiters and better enforcement, doctors and patients need to recognize the issue, and the technology that detects fake and substandard drugs needs to be cheaper and more robust. But Lieberman is optimistic that her cards will help, at least a little. “Sometimes you can’t solve the whole problem,” she says, “but you can start nibbling away at it.”