Past events, and unfortunately some recent ones, provide evidence of threats to the pharmaceutical supply chain. It is clear that excipients, active pharmaceutical ingredients (APIs), and pharmaceutical products can be counterfeited, contaminated, purposely mislabeled, and adulterated. Although the authors concentrate on excipients in this article, a review of incidents involving all of these product types and similar ones show the diversity of causes and the complexity involved in preventing these incidents. As reported by the World Health Organization, the Center for Medicines in the Public Interest predicts that counterfeit drug sales will reach $75 billion globally in 2010, an increase of more than 90% from 2005. Just as dangerous is the counterfeiting or contamination of the ingredients used to manufacture pharmaceutical products.

Recent deaths associated with heparin imported from China have drawn attention to APIs. The discovery of over-sulfated chondroitin in heparin was directly linked to some of the deaths. The speculation of how this chemical came to be in the API ranges from accidental contamination to purposeful adulteration to a change in the process for harvesting the heparin from pigs as a way to increase yield and reduce costs. These situations show the importance of the process for receiving and approving pharmaceutical starting materials in a fully integrated and robust quality system.

Table I: Select incidents involving adulterated ingredients.