USP Revises Excipient Standards to Limit Contamination

November 5, 2009
Pharmaceutical Technology Editors

ePT--the Electronic Newsletter of Pharmaceutical Technology

In response to a request from the US Food and Drug Administration, the US Pharmacopeial Convention (USP) revised its standards for propylene glycol and sorbitol solution

In response to a request from the US Food and Drug Administration, the US Pharmacopeial Convention (USP) revised its standards for propylene glycol and sorbitol solution, excipients widely used in prescription and over-the-counter drugs. The revised standards state that diethylene glycol (DEG) and ethylene glycol (EG) may not be present at a level above 0.10% of the excipients. The new standards also include tests for identifying these contaminants.

In addition, USP developed physical reference materials for the pharmaceutical excipients and impurities reference materials for DEG and EG. Manufacturers and regulators use these physical materials to confirm that a substance meets the USP written standards.

In the course of revising these standards, USP proposed new standards for sorbitol sorbitan solution and noncrystallizing sorbitol solution. The organization posted the four revised monograph standards on its website from July 1, 2009 to August 14, 2009 to allow manufacturers, regulators, and the public to review and comment on the proposed changes before the revisions were published formally. USP also held three open web meetings to explain the proposed revisions.

The revised standards for propylene glycol and sorbitol solution follow USP’s publication of an updated standard for glycerin, another pharmaceutical excipient. Like the two newest revisions, the updated glycerin standard is intended to limit contamination with DEG and EG. After a 12-week implementation period, the standards will become official on February 1, 2010. Manufacturers that use these pharmaceutical excipients in products marketed in the US will be required to comply with the new standards.

DEG is commonly used in antifreeze and should not be present in medicines. Several high-profile incidents of DEG contamination in cough syrups and other products have occurred in many countries. In July 2009, products contaminated with DEG were determined to be responsible for the deaths of at least 24 children in Bangladesh. Between November 2008 and January 2009, approximately 84 Nigerian children died after ingesting teething syrup contaminated with DEG.

“The adulteration of drugs and their ingredients is a critical public health issue,” said Susan de Mars, USP’s chief documentary standards officer, in a press release. “As recently as a few months ago, this was tragically illustrated in separate instances in Bangladesh and Nigeria. USP, in close collaboration with FDA, manufacturers, and other national and international parties, is addressing this by updating our standards for at-risk products. The unfortunate reality of economic incentives to counterfeit medicines makes this necessary.”

USP is a nonprofit scientific organization that sets legally recognized standards for the identity, quality, purity, strength, and consistency of prescription and over-the-counter medications and their ingredients in the United States. FDA enforces these standards.

See related Pharm Tech articles:
USP Announces New Standards for Heparin and Glycerin (ePT article)
FDA’s Sharfstein Addresses Industry (blog post)
Evaluating the Pieces of the Pharma Supply Chain (Pharm Tech)