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.
The most tragic incidents involving excipients have involved glycerin, an artificial sweetener (see Table I). These tragedies
were caused by diethylene glycol (DEG). Most cases of DEG poisonings are believed to have occurred because of pharmaceutical
counterfeits that contained glycerin (also known as glycerol), which is widely used in drug formulations and personal-care
products. DEG and glycerin are both clear, odorless, sweet-tasting liquids, but DEG is much easier and cheaper to manufacture.
As a result, DEG poisonings have typically occurred because of greed as well as poor quality control for receiving and approval
measures during the formulation and dispensing of medications.
Table I: Select incidents involving adulterated ingredients.
Other recent examples include toothpaste containing DEG and pet foods manufactured with wheat gluten contaminated with melamine.
These examples serve as clear warnings of threats to pharmaceutical supply chains and also provide insight into measures that
must be taken to avoid similar tragedies.