With the lure of large profits, low arrest risk, and relatively light sentences, it is no wonder that criminals are trafficking in counterfeit pharmaceuticals. Counterfeit drugs are broadly defined and include packages that may contain smaller amounts of active ingredients, counterfeit labels affixed to real pharmaceutical vials ("uplabeling"), labels with fake expiration dates, or even vials with bacterial contaminants. Since 2000, federal investigations of counterfeit drugs have increased fivefold, with counterfeiters targeting high-volume, expensive, and parenterally administered drugs.
The Prescription Drug Marketing Act of 1988 (PDMA) first addressed the problem of counterfeit drugs. However, the statute has had little practical effect on protecting the pharmaceutical supply chain. A requirement that all pharmaceutical transactions be accompanied by pedigrees outlining the routing history of the product was included in the PDMA and codified as a Federal regulation in 1999, but a stay on implementing this regulation has been in effect since then. In June 2006, the FDA indicated that it will vacate this stay in December 2006.Criminal activities may intersect with the pharmaceutical distribution system at numerous points because the system is so extensive and convoluted. Drugs are sold by manufacturers to one of three large national wholesalers (Cardinal, AmerisourceBergan, and McKesson), who sell them to regional wholesalers, who may sell them to a maze of secondary distributors (a so-called gray market), where counterfeiters have excellent opportunities to intercept the drug. At this point, counterfeiters can dilute, re-label, and repackage the drugs and then resell counterfeit products back to national wholesalers.
Reports and Investigations
The FDA reports that the annual number of investigations of suspected criminal pharmaceuticals has increased from 8 to 54 in the past 7 years. During that same time period, the FDA's MedWatch program received adverse event reports for only 45 patients who may have received counterfeit drugs. The largest number of reports (nine) concerned suspected counterfeit Epogen or Procrit (epoetin alfa). The MedWatch database included a small but increasing number of reports of loss of epoetin efficacy: 7 in 2000, 45 in 2001, and 139 in 2002 (when distribution of counterfeit Epogen and Procrit was at its peak).
Prompted by concerns over counterfeit Epogen and Procrit distribution in Florida, an investigative group called Operation Stone Cold was created in 2002 to coordinate the investigation of these counterfeit products. Tipped off by an owner of a Miami pharmacy, Operation Stone Cold investigated a wholesaler selling boxes of Epogen at $100 less than the wholesale price. The boxes contained 2,000 U/mL vials instead of the advertised 40,000 U/mL vials.
Amgen and Johnson & Johnson, manufacturers of Epogen and Procrit, respectively, issued warning letters to health care professionals describing counterfeit "uplabeled" vials and included the suspected lot numbers for the counterfeit vials it had located, pictures of the counterfeit labels, and descriptions of how the counterfeit products' labeling and packaging differed from those of the real product (see Table).