Excipient-Control Strategies

The authors outline excipient-control strategies and practices for the manufacture, distribution, and receipt of excipients.
Oct 01, 2008
Volume 2008 Supplement, Issue 5

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.
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.

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.

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