USP unveils measures to guard against excipient adulteration

The US Pharmacopeia is seeking comment on revisions to the monographs of four excipients considered at elevated risk of contamination with diethylene glycol (DEG) and ethylene glycol (EG).

USP has already revised its monograph for glycerin to take into account new identification methods designed to pick up adulteration with DEG, and has now extended this work to include monographs for propylene glycol, sorbitol solution, sorbitol sorbitan solution and non-crystallising sorbitol solution.

A revised monograph for another excipient at risk of DEG and EG adulteration – maltitol solution – will be prepared “in the near future”, said USP in a statement, saying it had undertaken the work at the specific request of the US Food and Drug Administration (FDA).

Contamination with DEG has been a factor in the majority of public health incidents involving several hundred deaths, generally as a result of failures in Good Manufacturing and Good Distribution Practices, in recent years.

As recently as last year, 84 children in Nigeria died after consuming a teething formula product containing glycerin contaminated with DEG, while in 2006 46 people died in Panama after taking a government-made cough syrup laced with the contaminant.

DEG contamination was also at fault in a 1996 case involving a cough syrup which killed 85 people in Haiti, while in 1990-1992 paracetamol syrup contaminated with DEG from propylene glycol led to 339 deaths in Bangladesh. In 1990, 47 people died in Nigeria after exposure to DEG in cough syrup.

The list is extensive yet likely does not account for all cases that have occurred.

USP held two open web-based meetings in March on propylene glycol and sorbitol solution to discuss method development for high-priority monographs, and expects to hold one more web meeting in August for further “informal comment.”

In addition to reference materials for the four excipient monographs, USP said it has developed two new impurities reference standards for DEG and EG to support these monograph revisions.

USP expects to issue a Revision Bulletin on October 30 and that the high-priority monographs will become official February 1, 2010, allowing for a 12-week implementation period.

Copies of the new methods are available for review here.

Meanwhile, the deadline for informal comments is August 14, 2009 and should be submitted to excipients@usp.org.