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Vetting Threats To Safe Drug Supplies

FDA-commissioned study seeks to characterize an insidious attack on public health

by Rick Mullin
April 2, 2012 | A version of this story appeared in Volume 90, Issue 14

Credit: Courtesy of Roger Bate
The box on the left is counterfeit; the one on the right is genuine.
Counterfeit (left) and legit Ciprotab.
Credit: Courtesy of Roger Bate
The box on the left is counterfeit; the one on the right is genuine.

A committee assembled by the Institute of Medicine of the National Academies to study the global public health implications of substandard, falsified, and counterfeit drugs held a preliminary forum on the topic in Washington, D.C., last month. Representatives from government, drug companies, and national and international law enforcement agencies struggled to characterize what all agree is a large, growing, and frustratingly nebulous threat to public health and safety.

The committee is preparing a study, commissioned by the Food & Drug Administration and due in early 2013, to help develop ways to assess risks posed by breaches in the global drug supply chain. Invited speakers discussed detection technologies as well as appropriate venues for collaboration among regulators, drugmakers, and government authorities. They also labored to clarify the distinction among substandard, falsified, and counterfeit medicines and debated how important the differences really are.

Participants in the day-and-a-half-long forum spent an entire morning on categorizing criminal activity. No consensus emerged on a topic that is much more than a technical quibble, because it determines such things as territorial jurisdiction and whether criminal activities must be pursued as violations of drug companies’ intellectual property or of public safety in affected countries.

Committee members agreed, however, that the drug supply chain is dangerously compromised by ineffective and unsafe drugs—everything from illegally manufactured Viagra sold on the Internet to adulterated drug ingredients such as the oversulfated derivative of chondroitin sulfate that killed more than 80 heparin users in the U.S. in 2008. The forum came on the heels of news that counterfeit Avastin, a drug used in cancer treatments, has been distributed in the U.S.

“FDA needs to acknowledge the incursion of a criminal element and work to mitigate the problem effectively,” said Mary Lou Valdez, associate commissioner for international programs at FDA. She cited the need for a better understanding of the global regulatory capacity.

Committee members, including physicians, lawyers, and health care professionals, examined the current detection and enforcement infrastructure. Each participated as an individual without representing current or past employers, which include the Bill & Melinda Gates Foundation, Georgetown University Law Center, the University of São Paulo School of Pharmaceutical Sciences, and Apple.

The most contentious discussion centered on the difference between counterfeit and falsified drugs. Roger Bate, an economist at the American Enterprise Institute who studies international health policy, said that counterfeiting is associated with a trademark violation, and falsification with willful misinformation on drug packaging. Saying he is not a stickler for how the terms are applied, Bate suggested that “counterfeit” might be established as a subset of falsified drugs, because all falsified drugs in the U.S. and Europe also violate trademarks.

Health care activists are concerned, however, that the lack of consensus over terms is hampering efforts to increase access to medicines in developing countries, according to Bate. And major drug companies, he said, have come under attack for withholding information on criminal activity and for focusing too narrowly on protecting intellectual property rather than public health.

Bate said large drug companies have withheld information from the public for what he thinks are both bad and good reasons. “Saying they want to avoid creating a panic is a point I don’t agree with,” he told C&EN. “But it often takes years for drug companies to build trust with regulatory agencies, customs, and police, and they have to promise not to disclose information to outside sources.”

Big pharma’s pursuit of counterfeiting as an intellectual property violation is understandable, Bate said, because no international health laws exist that would allow its companies to pursue criminals on charges of compromising public safety.

But Rohit Malpani, a senior campaigns adviser for Oxfam America, an international relief and development organization, told the committee that an excessive focus on intellectual property and trademarks has led to several unforeseen and negative side effects. One example he mentioned was a conflation of generic and counterfeit drugs, which has interfered with products reaching patients in poor countries. Developing countries are under increasing international pressure to establish laws and pursue criminals on the basis of intellectual property violations, he said. “Evidence has shown that an investment in strong regulatory authority and public health systems leads to better results,” Malpani told C&EN.

The heads of anticounterfeiting operations at Pfizer and Merck & Co. told the committee that their companies are aggressively pursuing threats to public health. Neither placed much store in the arguments over defining terms.

“I get a little upset when we get hung up on substandard, falsified, and counterfeit,” said John P. Clark, vice president of global security at Pfizer. “If something is represented as a Pfizer product and it is not made by Pfizer, we want it off the market.” Anthony L. Zook, director of anticounterfeiting at Merck, agreed. “Let’s not get bogged down in definitions,” Zook told the committee.

Both men detailed the complexity of policing the supply chain, the need to develop technologies to identify counterfeits, and the importance of working closely with law enforcement and regulatory agencies. They also underscored the dangers to public health.

“Counterfeiters put more time into packaging than they do into the product,” which can contain road paint, floor wax, and roach powder in lieu of active and inactive pharmaceutical ingredients, Clark said. Noting widespread counterfeiting of Pfizer’s erectile dysfunction drug Viagra, Clark said his biggest worry is online pharmacies selling illegitimate products.

Zook emphasized the complexity of the criminal networks involved. “Counterfeiters have supply chains just like Merck has supply chains,” he told the committee. Industry forensic intelligence groups are tasked with understanding a network of connections between criminal manufacturing, packaging, and distribution of drugs.

Linda I. Marks, senior litigation counsel at the Department of Justice’s Consumer Protection Branch, noted in a presentation to the committee that the Food, Drug & Cosmetic Act does not include the terms substandard, falsified, or counterfeit to describe unapproved drugs. “It’s sort of ‘tomayto, tomahto’ to us,” she said. “We are still able to charge perpetrators.” Marks pointed to three recent guilty pleas in a case where unapproved oncology drugs were distributed in the U.S. International criminal activity complicates policing the supply chain, however.

Jeffrey L. Gren, director of health and consumer goods at the Department of Commerce, outlined the department’s collaborative efforts, including the Joint Commission on Commerce & Trade that has worked on pharmaceutical oversight.

“But with all these initiatives, we are losing the battle,” he said. “There were more counterfeits in 2011 than there were in 2010, and I expect that there will be more in 2012.” Gren added, however, that it’s difficult to make more than broad directional observations about counterfeiting because of a lack of concrete data.

Others lamented the reliability of available data. Laurie A. Garrett, a senior fellow for global health at the independent Council on Foreign Relations, said the uneven regulatory and enforcement landscape impedes quantifying the problem of counterfeit drugs. “But our conclusion is that the problem is getting worse every day.”


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