WASHINGTON, DC—The recent incident in which the US Food and Drug Administration warned physicians of counterfeit bevacizumab—sold to multiple US cancer clinics—is only the latest high-profile example of the serious public health threat of substandard, falsified, or contaminated drugs. Initially a problem primarily in lifestyle drugs (such as weight loss products and those for erectile dysfunction), counterfeiting has now spread to drugs that can worsen illness or cause death. So said speakers at an Institute of Medicine meeting here, who emphasized that counterfeiting, exacerbated by multiple supply chain players in different countries and by Internet sales, has been identified in drugs for cancer, cardiovascular disease, and osteoporosis.
Counterfeit drugs are a growing concern for members of Congress, for professional societies, and for consumer/advocacy groups such as the Partnership for Safe Medicines coalition. An IOM committee is now probing the extent of the global counterfeiting problem and investigating approaches to fix it (see box) and intends to issue a report by the end of the year.
The committee is studying the issue at the request of the FDA. The public health aspect of counterfeit drugs—i.e., protecting patients—”is our passion,” said IOM Committee Chair Lawrence O. Gostin, JD, Professor of Law at Georgetown University, Professor of Public Health at Johns Hopkins University, and Director of the Center for Law & the Public's Health at Hopkins and Georgetown. He was also a member of the President's Task Force on National Health Care Reform.
What Sparked the Study?
Asked by OT if any one incident or event sparked the study, Katherine Bond, DSc, FDA Associate Director for Technical Cooperation and Capacity-Building, said no, but that “there is a general feeling that things are aligning” and that the counterfeiting problem needs a major, scientific focus.
“Globalization is a really fundamental change in the way the FDA works,” said another speaker, Jennifer Devine, JD, LLM, Deputy Director for Global Regulatory Operations & Policy at FDA. “We look upon it as, really, there is no border….In some ways this is very good, but it introduces a lot of risk and a lot of challenges.”
The IOM study on counterfeit drugs is especially important, she said, because today “a lot of the information that we have is very anecdotal.”
Asked if she believes the problem of drug counterfeiting is worsening, she said that part of the IOM committee's charge is to identify trends in global counterfeiting to answer that question. But, she said, one certainty is that the manufacturing of drugs from raw materials to consumer product is now far more complex—-opening many windows of opportunity for falsified products. “We recognize that the supply chain is a lot more complicated,” she said.
Added Anthony Zook, PhD, Director of Anti-Counterfeiting at Merck: “No product is immune; we really have no idea how large the problem is….Drug counterfeiting is attractive to criminals because it is very profitable.”
Speakers at the IOM meeting stressed that it is important to raise the public's awareness of the problem of counterfeit drugs, but also to strike a balance between engendering outright fear and healthy caution. With reference to the highly publicized bevacizumab warning, IOM committee member Daniel Carpenter, PhD, the Allie S. Freed Professor of Government and Director of the Center for American Political Studies at Harvard University, said that “public warnings can be blunt instruments that can create a crisis in confidence.”
At worst, a patient might stop his or her medicine. But, he noted, such blunt instruments can also give incentives to pharmaceutical companies to take extra steps to protect their supply chain. Asked if the IOM committee might be able to identify through statistical analysis geographical “hot spots” where drug counterfeiting is worse than in other areas, he said that should be possible eventually, but collecting such statistical data is now only in its infancy.
Fundamental Technological Detection Limitations
While multiple techniques can be used to try to identify drug imposters, “all technologies have fundamental detection limitations,” and no one technology can detect all counterfeits, said Mark Witkowski, PhD, Supervisory Chemist at the FDA's Trace Examination Section, Forensic Chemistry Center.
They are also expensive. “In a lot of cases, the packaging is where you're going to be able to detect the counterfeit,” he added, warning that today “many of the counterfeits are very good counterfeits.”
Agreeing with him was Lim Chin Chin, MSc, MBA, Director of the Forensic Chemistry & Physics Laboratory in the Forensic Science Division of the Health Sciences Authority in Singapore. “Some differences are very subtle,” she said of counterfeit drugs. “A visual inspection can be very misleading.” The content of the drug, its “chemical fingerprint,” is the most critical factor, she said.
Microscopy, Spectroscopy, Elemental Analysis, & Chromatography
Witkowski cited the following techniques as among those used to detect fake drugs: microscopy, spectroscopy, elemental analysis, and chromatography.
“You can use combination techniques to get the broadest coverage possible,” he noted. Today, there is a lot of pressure for fraud investigators to use portable counterfeit identification tools (such as hand-held spectrometers) in the field, he said, noting, though, that a field detection device must be easy to use and requires specialized training, and that a preliminary field identification of a counterfeit drug must then be confirmed in the laboratory.
“The goal is to secure the entire supply chain,” said Ashifi Gogo, PhD, Chief Executive Officer of Sproxil, which makes counterfeit detection technologies. He agreed with Witkowski about the importance of reliable detection technologies that can be used in the field. Among techniques for trying to ensure drug authenticity are barcodes and holograms, but sophisticated counterfeiters can easily copy holograms today, he warned.
Tablet Stamp Dye
Zook noted that a white tablet is the easiest to counterfeit, and that one way to tell a falsified drug from the real one is whether the tablet stamp dye is authentic. He noted that some countries have no laws against counterfeit drugs, but that they do have laws against trademark violations.
He urged strong punitive measures when drug counterfeiters are caught, to act as a deterrent to falsification. “Merck can identify bad guys; we have a lot of success in doing that….but we can't arrest anyone.”
What the IOM committee hopes to do is to identify technologies that could catch or prevent counterfeiting before it causes harm, said IOM committee member Patrick Lukulay, PhD, Director of the USAID-funded Promoting the Quality of Medicines program, which is implemented by the United States Pharmacopeia. Unfortunately today, though, he said, “most of what we're seeing is reactive: action after several people have died.”
Aims of the Study
The IOM committee hopes to:
1. Identify global counterfeit trends, using the available literature, including differences and similarities in different regions of the globe.
2. Identify methodologies to estimate falsified, substandard, or counterfeit medicines as a risk factor for harm to patients, and monitor its global health impact.
3. Identify areas where harmonization of standards could contribute to stronger regulatory actions.
4. Identify key gaps in evidence, detection, and sampling methodologies and analytical techniques, and areas where harmonized approaches could contribute to more evidence-based methods in addressing key issues regarding safe medicines.
5. Assess the effectiveness of global regulatory approaches, including prevention, detection (track and trace), and compliance and enforcement actions—and, where possible, assess their contributions to reducing the pubic health impact of substandard, falsified, and counterfeit drugs.
6. Based on the assessment described above, identify areas where collaboration among key stakeholders—government and industry, for example—might help to reduce the global burden of counterfeit drugs.
7. Recommend a collaborative path forward regionally and globally in a way that is sensitive to the concerns of international regulators.
© 2012 Lippincott Williams & Wilkins, Inc.