In the U.S. it’s uncommon to encounter counterfeit pharmaceuticals, drugs that are manufactured illegally and passed off as the genuine articles. But in countries with weaker regulatory systems such as India and Nigeria these drugs make up 25 to 70 percent of the pharmaceuticals available to consumers. In 2010 counterfeit drugs made up a $75-billion industry, one that only seems to be growing. Because the majority of these drugs—intended to treat patients—contain too much or too little of the active ingredient, anywhere from 100,000 to one million people die every year worldwide.
Pharmaceutical companies and government regulators are continually looking for ways to mark genuine drugs and detect phonies. Now a biotech company called Applied DNA Sciences may have an original solution: tagging legitimate drugs with engineered DNA. Each unit of pharmaceutical would contain a unique genetic signature that authorities could detect with basic chemical assessments. The tactic has worked in other industries with complex supply chains such as textiles, and the DNA could be incorporated into the drugs while falling within the strict U.S. Food and Drug Administration regulations for how the DNA is safely incorporated. Now all that remains is for pharmaceutical companies to put the solution into action. “If you consider the morbidity and mortality caused by the scourge of counterfeit drugs, it is an urgent problem that requires a global response,” says Jim Hayward, the CEO of Applied DNA Sciences. “And that should begin at the level of the [pharmaceutical] industry.”
Applied DNA Sciences calls its technique SigNature DNA, which could be used in myriad products in addition to pharmaceuticals. To make the DNA tags scientists extract genetic code from plants and reassemble it to be distinct from any other DNA on the planet. That unique code can be embedded into ink, fabric, plastic, vapor or metal, depending on the product in question, without adding another step in the manufacturing process. The amount of DNA needed to tag drugs is so small, Hayward says, that it would have no effect on a person when ingested. Furthermore, the DNA will not break down for years, making the markers useful for items with long shelf lives. The company also created a device to detect the presence of the DNA tag, based on polymerase chain reaction (PCR), a test so fundamental to chemistry that it is used in high school science labs across the country.
The technology could be a game changer for pharmaceuticals. To keep it simple, manufacturers could simply tag the drug’s active ingredient and the tests would reveal if the final product contains the marker. But counterfeiters do not always just switch out the active ingredients—they could modify agents such as binders, fillers, coatings or inks—so manufacturers might want to tag each component, giving every drug a unique “product genome,” as Hayward calls it. “You’ve got a variety of markers that designate each component of [a] pressed tablet, and they can show each one’s relative concentration,” he adds. The company keeps a database linking each tag to the date and type of product, which could help thwart criminals trying to sell pharmaceuticals past their expiration dates.
The ability to unequivocally track and identify drugs would be useful for pharmaceutical firms, which spend millions of dollars per year for aggressive legal teams to find and prosecute counterfeiters. But it is also good for enforcement organizations like border control agents, INTERPOL and the World Health Organization, all of which are continually monitoring the authenticity of imported drugs. The pharma industry is increasingly international—ingredients from India might be mixed in China, then the product hopscotches across a handful of countries before reaching a pharmacy. When drugs come into the U.S., the FDA and border control officials work to verify the authenticity of as many compounds as possible. That can be hard to do if, for example, officials did not know that a company changed the formulation of a particular drug. But it would not be difficult if officials could catch a fake simply by running it through a PCR. The tags could be even more useful for officials in developing countries where a lack of government funding puts border control agents in short supply, and those that are present may be liable to accept bribes from counterfeiters.
Hayward and his colleagues think the tags could reduce counterfeit pharmaceuticals because similar markers have worked in other industries. Genetic tests have shown that many garments labeled as 100 percent pima cotton, a high-end and expensive strain, were often mixed with other, lower-grade cottons by the time they ended up in stores. When Applied DNA Sciences tagged the pima cotton and tested the fabric after it was ginned, spun, woven and dyed abroad, textile companies could be sure that the product that ended up on shelves in the U.S. was in fact made of the fabric its label claimed. “We measure our success by what came back to the U.S. and made it to retailer shelves,” Hayward says—garments were truly 100 percent pima cotton for the first time in recent memory. The Department of Defense also used SigNature DNA tags to eradicate counterfeit electronic parts that ended up in U.S. aircraft.
Despite successes with other products, there is one big difference between drugs and, say, textiles or aircraft components. Drugs have a delicate chemical balance, and are ingested into or applied to the body. Adding even a little extra genetic code could change a compound’s stability, how it is released into the body or the efficacy of its active ingredient, says Vincent Remcho, a chemistry professor at Oregon State University. Hayward says that such a tiny amount of DNA would not throw off this balance, but researchers and regulators would need to see safety studies to confirm this. However, “if all of these factors can be successfully addressed, this approach to authentication could be quite useful; clearly there is a need for effective means of authentication of pharmaceuticals,” he adds.
Furthermore, government regulations could make it prohibitively complicated (and expensive) to add DNA to a compound, says Rick Sachleben, a researcher in the pharmaceutical industry and a member of the American Chemical Society experts panel. To comply with FDA rules, anytime a pharmaceutical company changes a formula or component, it needs to prove the drug is just as safe and effective as its previous version, leading to expensive clinical trials. To incorporate DNA to the active ingredient, Sachleben says, a company would essentially have to reformulate its drug, which would be exorbitantly expensive. “DNA tags are possible but there’s still high regulatory burden to do that,” Sachleben says. “Most drug companies will say, ‘My drug is on the market and I’m not going to play with that.’”
That high regulatory burden is likely the reason why most other anticounterfeiting techniques such as scratch-off labels or 3-D bar codes are limited to packaging or a pill’s surface. Applied DNA Sciences has already overcome most regulatory hurdles, Hayward says, because its system fits within the narrow scope of anticounterfeiting tagging measures issued by the FDA in 2011. “We are fully compliant with that guideline. There is no hurdle to implementation, only adoption,” Hayward adds.
The company is starting to approach pharmaceutical manufacturers with SigNature DNA tags. Hayward could not be specific about the cost of the technique but he says it would not affect the final price of a drug—it is “quite affordable” even for textile companies that are not as flush with cash as the pharma giants.
Even if the cost is as low as Hayward claims, Sachleben agrees that adoption will likely be the biggest obstacle—pharmaceutical companies might have to conduct safety experiments or even clinical trials, after which they would only be able to add the tags to solid pills and not sprays or liquids to adhere to the FDA guideline. Unlike competing technologies such as scratch-off labels, patients could not verify if a drug was authentic, they would have to rely on officials to crack down, which might not be so reliable in developing countries where fakes and bribery of officials are common. And although synthetic DNA is certainly not easy to replicate, no anticounterfeiting technique is foolproof. “There’s nothing stopping any pharmaceutical company from implementing this. [Applied DNA Sciences] just has to convince a risk-averse, highly regulated industry to adopt new technology, and there’s always a challenge in that,” Sachleben says.
Hayward and his colleagues, however, see a future full of opportunity. “Virtually everyone we talked to in the [pharmaceutical] industry responds with great gusto and interest—DNA tagging triggers all kinds of imagination and creativity,” Hayward says.
Implementing high-tech methods to better deter counterfeiters is a good place to start, and “if anticounterfeiting tech becomes important enough, then these guys are going to be out there competing with the other technologies,” Sachleben says. “And in the end, usually the best technology wins.”