ABSTRACT
Counterfeit and unapproved drugs pose serious health risks to patients in the United States. High-profile cases, such as the incident concerning the counterfeit version of the oncology drug Avastin, demonstrate that there are major incentives such as demand, convenience, high profit, and low legal risks for rogue wholesale distributors to sell unapproved and counterfeit drugs. Wholesale drug distributors play a significant role in ensuring prescription medications are delivered safely and efficiently to health care practitioners and pharmacies. While the U.S. drug supply chain is one of the most secure and sophisticated in the world, there are networks of rogue wholesale drug distributors that target physicians and medical practices by advertising prescription drugs for sale at deeply discounted rates. Buying drugs from unlicensed sources puts patients at risk of consuming medications that may be unapproved, counterfeit, contaminated, or ineffective. It is critical that physicians be aware of the patient health risks and potential legal consequences of purchasing drugs from illegal sources. State medical boards can help address this issue given their important role of public protection in the licensing and oversight of the practice of medicine. The regulatory community serves as a key information hub and can provide targeted communication channels to educate physicians.
Rogue wholesale drug distributors target physicians using aggressive marketing tactics and offering medications at deeply discounted rates. For years the U.S. Food and Drug Administration (FDA) has responded to these breaches in the U.S. drug supply chain, which expose patients to drugs that:
May be counterfeit, contaminated, ineffective, or otherwise unsafe.
May not have been evaluated by the FDA for safety and efficacy.
May not contain the appropriate amount of active ingredients.
May contain harmful ingredients.
In 2012, for example, the FDA warned health care professionals about two different counterfeit versions of injectable oncology medications containing the active ingredient bevacizumab. In February 2012, the FDA issued a statement concerning a counterfeit product, labeled as Avastin under the Roche logo, which did not have any active ingredient.1 Although Avastin manufactured by Roche is approved for marketing outside of the United States, the only FDA-approved version of Avastin for use in the United States is marketed by Genentech (a member company of the Roche Group) and carries the Genentech logo on the packaging. This case was particularly concerning given the vulnerable patient population in which lack of appropriate treatment can result in cancer progression and/or serious adverse effects. In fact, one cancer patient was rushed to the hospital after receiving an infusion of tap water containing mold instead of genuine Avastin. Photos of the counterfeit product are available at https://wayback.archive-it.org/7993/20170722160606/https://www.fda.gov/Drugs/DrugSafety/ucm291960.htm
In April 2012, the FDA issued a statement that counterfeit versions of the Turkey-approved Roche injectable oncology drug Altuzan had been purchased by U.S. medical practices.2 While Altuzan also has the active ingredient bevacizumab, it is not approved by the FDA in the United States. In addition, the counterfeit version of Altuzan did not contain any active ingredient. An oncology nurse in the United States reported that two patients had “immediate bad reactions” during infusions of Altuzan. One of these patients who had been treated with Avastin started to shake in the middle of being transfused and had to be disconnected from treatment.3
ROGUE WHOLESALE DRUG DISTRIBUTORS TARGET DOCTORS USING AGGRESSIVE MARKETING TACTICS AND OFFERING MEDICATIONS AT DEEPLY DISCOUNTED RATES.
Counterfeits are not limited to oncology drugs. In 2015, a counterfeit version of Botox entered the legitimate U.S. supply chain.4 The product was sold by an unlicensed supplier that was not authorized to ship or distribute drug products in the United States. Both the outer carton and vial on the suspect product were counterfeit. The lot number was missing on the vial of the counterfeit product, and the outer carton and vial displayed the active ingredient as “Botulinum Toxin Type A” instead of “OnabotulinumtoxinA.”4
These examples illustrate the significant public health concern, especially to vulnerable patient populations, when unapproved drugs are purchased from rogue sources. Several of these drugs are associated with serious risks, and the FDA-approved drug carries a black box warning, the strongest warning the FDA issues on product labeling, indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. Some drugs also have specific shipping and handling requirements (e.g., cold chain products such as Botox). When such products are purchased outside of the legitimate U.S. drug supply chain, there is no guarantee they were manufactured, transported or handled under proper storage conditions.
ROGUE WHOLESALE DISTRIBUTORS APPEAR TO PRIMARILY SELL ONCOLOGY AND COSMETIC DERMATOLOGY DRUGS AND MEDICAL DEVICES THAT ARE ADMINISTERED TO PATIENTS BY A PHYSICIAN OR OTHER HEALTH CARE PRACTITIONER.
Important signs of counterfeit prescription drugs that physicians should be aware of are depicted in Table 1.
Signs of Counterfeiting
Scope of the Problem
Rogue wholesale distributors appear to primarily sell oncology and cosmetic dermatology drugs and medical devices that are administered to patients by a physician or other health care practitioner. The FDA aggressively pursues all those who seek to profit from the importation and distribution of such drugs. In many cases, the FDA has seized these unapproved products and tested the substances to determine whether patients may have received counterfeit versions of FDA-approved medications. Since 2012, the FDA has sent letters notifying nearly 3,500 physicians5 that they purchased drugs from distributors that imported counterfeit and/or unapproved drugs into the U.S. Because the FDA recognizes the critical role of state regulatory authorities in the oversight of the practice of medicine, it routinely copies the respective state medical boards on these letters to share this important patient safety information. In addition, since 2012 the FDA has identified more than 15 distributors who have engaged in these unlawful practices. The table below depicts examples of drugs purchased by medical clinics in the United States from rogue distributors, with oncology and dermatology being the most common therapeutic areas targeted.
Protecting Patients and the Drug Supply Chain
In keeping with the Drug Supply Chain Security Act (DSCSA)6, the FDA uses a multi-prong approach — prevention, detection, and response — to address threats to the U.S. drug supply chain. Prevention focuses on reducing the manufacturing of counterfeit and substandard products, improving supply chain integrity by ensuring transparency and accountability, and enhances regulatory infrastructure and oversight. Detection includes improved surveillance, ensuring the laboratory capacity exists for expedient and efficient confirmation of counterfeit drugs, and leveraging advanced technologies, such as the FDA's CD-3 device, to detect counterfeit drugs in transit. The CD-3 tool contains a library of information about authentic drugs and the packaging in which they come. It allows FDA investigators to compare authentic images of a product with the suspect product, instantaneously showing clear differences between suspect and authentic products that would not have been clear to the naked eye. Response encompasses swift and effective communication to health care providers and the public of confirmed counterfeit incidents, efficient removal of counterfeit products from the market, and enhanced enforcement activities and tools to tackle the problem. The FDA's Office of Criminal Investigations also pursues criminal enterprises involved in drug counterfeiting and other activities to secure the U.S. supply chain.
Consequences for Physicians
Physicians who purchase drugs from illegal, unlicensed sources are putting patients at risk and are also breaking the law. They may be subject to criminal investigations by the FDA's Office of Criminal Investigations and prosecution by the U.S. Department of Justice (DOJ). In fact, since 2012, DOJ has prosecuted more than 95 corporations and individuals, including physicians, for criminal charges related to selling unapproved drugs or receiving and administering unapproved drugs to patients. These criminal convictions have resulted in jail time and/or fines of millions of dollars.
One recent case is that of oncologist Anda Norbergs, MD, from Palm Harbor, Florida, who bought unapproved cancer drugs from foreign, unlicensed distributors. In 2012, the FDA sent a letter to Dr. Norbergs regarding the risks of purchasing medications from foreign or unlicensed suppliers and indicating that a counterfeit version of Roche's Altuzan from a foreign distributor had been found in the United States. The letter requested that Dr. Norbergs cease using products from foreign or unlicensed sources. However, Dr. Norbergs continued these illegal purchasing practices. In November 2016, she was found guilty of 17 counts of receipt and delivery of misbranded drugs, 12 counts of smuggling goods into the United States, 11 counts of health care fraud, and five counts of mail fraud. In August 2017, Dr. Norbergs was sentenced to nearly six years in federal prison for treating patients with unapproved oncology medications. As part of her sentence, the court also entered a money judgment for $848,671.19, the proceeds of the criminal conduct.7 Dr. Norbergs no longer holds a medical license.
IT IS IMPORTANT THAT PHYSICIANS BE AWARE OF THE RISKS TO THEIR PATIENTS; THE THREATS TO THE SECURITY OF THE U.S. DRUG SUPPLY CHAIN; AND THE POTENTIAL FOR SERIOUS LEGAL CONSEQUENCES FOR ENGAGING IN ILLEGAL PRACTICES.
How Physicians Can Avoid Trouble
Physicians can take the following steps to help ensure the drugs they purchase and administer to patients are safe, effective, and meet U.S. standards for quality:
Verify the wholesale drug distributor is properly licensed in the state(s) where it is conducting business by using the link to the state databases at www.fda.gov/Drugs/DrugSafety/DrugIntegrity-andSupplyChainSecurity/ucm281446.htm. The Drug Supply Chain Security Act requires physicians to purchase prescription drugs from licensed wholesale distributors.
Perform due diligence to ensure that the drugs they purchase are FDA-approved. Beware of offers that are too good to be true.
Pay close attention to patient feedback, including several patients reporting a new adverse event or lack of therapeutic effect from the same product. Physicians and patients should report adverse events related to the use of a suspect product and drug quality issues to the FDA's MedWatch Safety Information and Adverse Event Reporting Program. Suspicious activity can be reported to the FDA's Office of Criminal Investigations at www.fda.gov/oci.
Ensure all staff responsible for the procurement and distribution of medications to patients, including practice managers and nurses, are trained on safe purchasing practices.
Once a physician receives a drug for patient administration, additional precautions should be taken to ensure that the product is FDA-approved (see Table 1: Signs of Counterfeiting).
In addition, if the package appears to be suspicious, physicians can contact the manufacturer to report concerns and determine if the product is authentic or counterfeit.
Role of State Medical Boards
State medical boards can play an important role in helping physicians understand the risks of purchasing from illegitimate distributors and how to identify patient safety concerns by:
Using communication channels, such as newsletters and mailings, to disseminate information to physicians regarding the dangers of counterfeit drugs.
Considering prescription drug counterfeiting as a potential topic for webinars and continuing medical education (CE) for licensees.
Utilizing the FDA's web resources on “Know Your Source: Protecting Patients from Unsafe Drugs” available at https://www.fda.gov/Drugs/ResourcesForYou/HealthProfessionals/ucm389121.htm.
State medical boards are also encouraged to share any research or surveillance related to harm that has resulted from patients receiving counterfeit prescription medications from their physicians to the FDA at [email protected].
Conclusion
Unfortunately, rogue wholesale drug distributors do not have the patient's best interest in mind and will readily profit from the sale of unapproved, substandard, foreign, and counterfeit medications in the United States. It is important that physicians be aware of the risks to their patients, the threats to the security of the U.S. drug supply chain, and the potential for serious legal consequences for engaging in illegal practices. The overall goal is to ensure physicians purchase FDA-approved prescription medications from distributors within the legitimate U.S. supply chain, so that patients receive only safe and effective drugs.
About the Authors
↵Eleni Anagnostiadis, RPh, MPM, is Director, Division of Supply Chain Integrity, U.S. Food and Drug Administration. She is also a Commander in the U.S. Public Health Service Commissioned Corps.
↵Sangeeta V. Chatterjee, PharmD, is Branch Chief, Supply Chain Response and Enforcement Branch, Division of Supply Chain Integrity, U.S. Food and Drug Administration.
- Copyright 2018 Federation of State Medical Boards. All Rights Reserved.
References
- 1.↵U.S. Food and Drug Administration. Counterfeit Version of Avastin in U.S. Distribution. February14, 2012. Accessible at: https://wayback.archive-it.org/7993/20170722160606/https://www.fda.gov/Drugs/DrugSafety/ucm291960.htm
- 2.↵U.S. Food and Drug Administration. Another Counterfeit Cancer Medicine found in U.S.- Illegal Practice Puts Patients at Risk. April3, 2012. Accessible at: https://wayback.archive-it.org/7993/20170406013350/https://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/ucm298047.htm.
- 3.↵U.S. Department of Justice news release. English Citizen Sentenced for Distributing Adulterated and Counterfeit Cancer Drugs. July11, 2013. Accessible at: https://www.justice.gov/usao-edmo/pr/english-citizen-sentenced-distributing-adulterated-and-counterfeit-cancer-drugs.
- 4.↵U.S. Food and Drug Administration. Counterfeit Version of Botox Found in the United States. April16, 2015. Accessible at: https://www.fda.gov/drugs/drugsafety/ucm443217.htm.
- 5.↵U.S. Food and Drug Administration. Notice to Physicians. Accessible at: www.fda.gov/downloads/drugs/resources-foryou/healthprofessionals/ucm529697.pdf.
- 6.↵U.S. Drug Supply Chain Security Act (DSCSA), Title II. Enacted November 27, 2013. Accessible at: https://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/DrugSupplyChainSecurityAct//.
- 7.↵U.S. Department of Justice news release. Palm Harbor Oncologist Sentenced to Nearly Six Years for Treating Patients With Unapproved Cancer Drugs. August7, 2017. Accessible at: www.justice.gov/usao-mdfl/pr/palm-harbor-oncologist-sentenced-nearly-six-years-treating-patients-unapproved-cancer
