Anticounterfeiting And NIR: A Hong Kong Diary

Many people in the world today will never know whether the drugs they’re taking are genuine. In some parts of the world, including many African nations, China, India and Russia, the odds are increasing that your next prescription will be filled with counterfeit medicine.

Today, nearly $39 billion worth of fake drugs are sold each year, roughly 11% of the total annual global. The Center for Medicines in the Public Interest expects this figure to reach $75 billion by 2010. The scope of the counterfeiting problem varies widely by country. Pharmacy sales in the U.S. can be expected to be genuine, and 99% of them are, according to estimates by the World Health Organization (WHO).

However, the case is very different for drugs that U.S. citizens buy on the Internet, roughly half of which are likely to be fake. In Angola and Nigeria, up to 70% of the drug supply is likely counterfeit, according to WHO’s International Medical Products Anti-Counterfeiting Taskforce (IMPACT). In parts of Africa, Asia and Latin America, the figure is over 30%, IMPACT estimates, while in some former Soviet republics, it is higher than 20%; in developing nations it is, on average, over 10%.

No Time for Complacency

According to the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), counterfeiting is greater in those regions where regulatory and legal oversight is weaker. However, the diminished presence of fakes in developed countries with effective regulatory systems and market control (such as the U.S., EU, Australia, Canada, Japan and New Zealand) should not be a cause for complacency, since the trend is toward an increase in counterfeit medicines even in developed countries.

In May 2007, the FDA issued a report warning of counterfeits on the Internet. This followed a 2006 warning about Internet counterfeits of Lipitor, Diovan, Actonel, Nexium, Hyzaar, Ezetrol (known as Zetia in the United States), Crestor, Celebrex, Arimidex, and Propecia. The 2007 report cited Xenical, a Roche weight-loss drug, that contained either no active ingredient, or a different active ingredient, sibutramine. Other cases involved Tamifu and Cialis. These cases fit the typical drug counterfeiting profile: the drugs are relatively expensive, and, in the case of Tamiflu, they may be in short supply.

A wide variety of product protection technologies have been developed for use on pharmaceutical products. Overt verification tools, such as holograms or color-shifting ink, can be seen by consumers. Unfortunately, they are relatively easy to copy. Covert tools, such as invisible printing and digital watermarks, are more expensive and require special devices to check. There is a movement to make the verification easier, whether it is by UV light, or via a camera phone as used by YottaMark.

However, both overt and covert methods tag the package, rather than the product. And both rely on a kind of “arms-race” approach to protection, based on the assumption that the more expensive and complex the technology, the less likely the counterfeiter is to use it. There are obvious flaws to this approach: it makes sense only on expensive drugs, and as counterfeiters become increasingly sophisticated, and the cost of technologies drops, manufacturers are forced to select more and more expensive countermeasures.

Lab-based techniques, including near-infrared, mid-infrared, and Raman spectroscopy, X-ray powder diffraction, thermal gravimetric analysis, microscopy and various forms of chromatography have been used to check the authenticity of samples. Although powerful, these tend to be slow, limiting their use in prosecution of counterfeiting. Forensic technology, essentially chemical or biological tags built into medicines or packaging, are even more secure, but often significantly more costly.

Serialization or track-and-trace systems, using technologies such as bar codes and radio frequency identification (RFID), help provide authentication by allowing a medicine to be tracked through the supply chain. These require an expensive technical infrastructure and are not completely immune to “hacking.” There is still some uncertainty about RFID interaction with liquids and biologics.

Furthermore, RFID tracks the pallet and the package, but not the drug itself, and, before it reaches the consumer, the tag is removed. There are now documented cases in which an RFID-tagged package has been shown to contain counterfeit product, as noted by Novartis’s CSO James Christian in an article published last year in CIO magazine (see References).

The European Federation of Pharmaceutical Industries and Associations (EFPIA) announced last May that it had selected the 2-D barcode as the preferred anti-counterfeit tool “instead of the less reliable and more expensive RFID.” These technologies cannot stop counterfeiting on their own. RFID is indeed expensive, and the whole armsrace approach will be unable to protect less-expensive products, whether drugs destined for developing world markets, or generics for developed countries.

Anti-counterfeiting, for better or for worse, is likely to be a growth business for years to come, with increasing opportunities for less expensive solutions. In an attempt to investigate the counterfeiting problem firsthand, I took some time during a trip to Hong Kong to seek out counterfeit products. Counterfeit luxury goods were everywhere. Pharmaceuticals were harder to track down.

Shopping For Counterfeits in Hong Kong

Counterfeit medicines are not being peddled in flea markets in Hong Kong. Instead, they are sold in regular shops, alongside legitimate Chinese and Western medicines. The shops are clean, with shining glass counters, and are staffed by pharmacists, some more knowledgeable than others. The fake drugs come in packages that look real, and sometimes they are even covered with special “anticounterfeiting” tapes and stickers.

The good news? It took some work to find counterfeits. The bad news? I found plenty. Since I didn’t speak Chinese, I presented my list of medicines. I went for the easy choices: although AIDS drugs, growth hormone, cancer drugs, and pain preparations are heavily counterfeited, nobody had those when I requested them (my initial list included Combivir, Diflucan, Epivir, Epogen, Procrit, Serostim, and Sustiva). So mostly I asked for medicines that a healthy person might buy in a drug store: Norvasc, Lipitor, Lamisil, Viagra, Cialis, and Levitra. None of the shops with herbal ingredients had them, but in one case a gesturing gentleman eagerly transcended the language barrier and walked me down the street a couple of store fronts to the larger shop that he thought could help me.

In Hong Kong markets, Western medicines are always displayed separately from traditional Chinese medicines. In some shops, herbal and animal ingredients and supplements are displayed openly, where packaged pharmaceuticals are generally kept in glass display cases.

There amidst the shampoos, toothpastes, tiger extracts and liquor products, there were in fact some Western medicines. But buying them wasn’t like shopping in a pharmacy in the United States. There were many single-dose packages: one pill, or two or four. One package, of Pepzan, an H2 blocker made in New Zealand, was open. It contained a blister pack of 15 tablets, although the package claimed it contained 120 tablets. The price, written in pen on the flap, was HK$110 – a bit much, but I bought it. The cashier charged me HK$15 – the price for the partial pack, of course. I also found a pack of Viagra – one 50mg tablet, for HK$95. It looked like a genuine Pfizer product, with a blue Pfizer sticker on it, but nobody asked me any questions about prescriptions or why I, a woman, was buying it.

I had the list of top counterfeited drugs on my PDA, and I handed it to one English-speaking pharmacist and said I was interested in all of the drugs on the list. He handled the PDA with reverence, and pushed a few buttons, before handing it back and saying he didn’t have any of those drugs. From the look on his face, I could tell he was wondering why I was using a computer for something I could have accomplished with a piece of paper.

The pharmacies that did sell Western drugs were all glassfronted, with glass display cases, and all tiny by American standards, about 10’ x 12’. Many had “No Fakes” pledges on their windows, and many had displays claiming to be authorized dealers for Pfizer and Lilly. I asked for Norvasc, Lipitor, Lamisil, Viagra, Cialis, and Levitra, and found them all. In one case, a single shop had everything, and the pharmacist spoke excellent English. He wrote down his prices on my paper. All the products appeared genuine – or at least consistent with what I’d seen elsewhere.

And the pharmacist, finally, was curious: What was I doing asking for all these different drugs? I confessed that I was actually looking for counterfeits. His reply? “Do you work for Pfizer?” Then he asked if I was a journalist – and I explained that I worked for a company that could detect counterfeit pills, not just packages, and was looking for test materials. Still wary, he explained that I was in the wrong neighborhood. Sham Shui Po, on Kowloon, is a good place to buy genuine medicine, he said, but if you want counterfeits, you need to go where the tourists are.

The Hong Kong resident who buys a counterfeit, he said, will come back to your shop and complain. Tourists won’t. Western tourists who are looking for a bargain shop in the dispensaries near the tourist markets (themselves full of counterfeit watches, purses, and other designer goods). Visitors from mainland China also buy counterfeits, to resell in China.

I asked how to tell which shops had counterfeits. Would they be the ones without a ‘No Fakes’ pledge or authorized dealer stickers? Not at all: if you buy even one pill legally, you get a sticker, and the rest of your inventory may not be genuine. Price is the key. The profit margin on pharmaceuticals is thin, about HK$10, a little more than a dollar. So no one will bargain much on genuine product, because they’d lose money. He suggested that I offer to buy five or six, and see if the price started to move.

We recalled an episode the previous day, when an enthusiastic pharmacist had tried to sell us an expensive bottle of Viagra, at HK$2400. Not having sufficient cash, we wavered and finally left. He chased us out the door, offering lower and lower prices. We resolved to try to find that shop again. We went back to the Yau Ma Tei tourist area of Kowloon, and used the paper that was now annotated with our Sham Shui Po pharmacist’s prices.

In the first few dispensaries, the prices varied little and the products looked consistent, so we thanked the proprietors but did not buy much. We did watch, mesmerized, as one used a hair dryer and plastic wrap to shrink-wrap packages. Many of the Western products we saw had stickers on them. Some were logos, with or without holograms. Some carried printed information that covered up different printed information. A few of the boxes were shrink-wrapped, although we couldn’t tell whether that was homegrown or not.

At last we found the over-eager Viagra seller. He was happy to see us: we were big spenders. He had Cialis, too, a big shrink-wrapped set of little white and green 4-pack boxes of 20mg pills. Since I already had one from another pharmacy, and since they all looked the same, I asked for a different container size. He pulled out a silver box with a 50mg dose. I didn’t remember Lilly making a 50mg dose, so I examined it carefully.

It said Tadalafil in big letters and Cialis in little letters – unlike any American drug I’d ever seen, the generic name was bigger than the brand name. It had a nice Lilly hologram sticker on it, but on the other side of the box, the name was, in the right red loopy script, Lieel, not Lilly. Trying to sound casual, I started to bargain. We added the Viagra bottle back in, also at a discount. It looked dingy instead of bright white, and was missing its box, but it didn’t provide any obvious red flags.

Hong Kong has cracked down on counterfeit pharmaceuticals, and many people told me the situation there was now much better, “not like China.” But there are clearly fakes in the marketplace, along with diverted perfume in little bottles marked “Sample, Not to be Sold,” and Thai-labeled Colgate toothpaste in a flavor I’m not sure Colgate actually makes. These are not being sold in stalls in street markets, but in stores, some of them chain stores, in the center of the city. Caveat emptor, or “let the buyer beware,” as the ancient Romans said. But these days, not just the buyer but the manufacturer, must be vigilant.

References

Dubois, Janie, Jean-Claude Wolff, John K. Warrack, Joseph Schoppelrei and E. Neil Lewis, “NIR Chemical Imaging for Counterfeit Pharmaceutical Products Analysis,” Spectroscopy, Feb. 1, 2007.

FDA Counterfeit Drug Task Force Report, June 2006, http://www.fda.gov/oc/initiatives/ counterfeit/report6_06.html

“FDA Warns Consumers about Counterfeit Drugs from Multiple Internet Sellers,” May 2007: http://www.fda.gov/bbs/topics/ NEWS/2007/NEW01623.html

Polli, J.E. and Hoag, S.W. (2004): Near-Infrared Technology Detects Counterfeit Drugs. US Pharmacist Feb:104-6.

Scafi, S.H.F. and Pasquini, C., Identification of counterfeit drugs using near-infrared spectroscopy, Analyst, 2001, 126, 2218-2224. Scalet, Sarah D. (2007): Radio-Frequency ID (RFID) as an Answer to Pharmaceutical Drug Counterfeiting: Five myths about how Radio-Frequency ID (RFID) technology will stop counterfeit drugs. CIO Magazine, 5/11/07.

Yoon, W.L., Jee, R.D., Charvill, A., Lee, G. and Mo at, A.C., Application of nearinfrared spectroscopy to the determination of the sites of manufacture of proprietary products, J. Biomed. Pharm. Analysis, 2004, 34, 933-944.

Yoon, W. L. “Near-Infrared Spectroscopy: A Novel Tool to Detect Pharmaceutical Counterfeits,” available from Beecham Pharmaceutical Technologies Service, http://www.bpts-pharm.com/gw02.htm.