Type of Posting: General Announcement
Posting Date: 28-Feb-2025
Expert Committee: Complex Excipients
Since 1937, there have been numerous reports of diethylene glycol (DEG) and/or ethylene glycol (EG) poisoning issues. In the beginning of 2023, WHO issued an alert regarding DEG/EG contamination and adulteration that occurred in multiple countries resulting in more than 300 fatalities, most of whom were children. In May 2023, the U.S. U.S. Food and Drug Administration (FDA) issued a Guidance for Industry - Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol, in which seven previously revised USP-NF excipient monographs with a high risk of EG/DEG contamination/adulteration were referenced.
To help address these risks, the Complex Excipients Expert Committee (CE EC) published the USP-NF PEG monograph revision proposal through an accelerated revision process – Interim Revision Announcement (IRA) in PF 50(3) [May – Jun. 2024] by including the Limit of Ethylene Glycol and Diethylene Glycol test in the Identification (ID) section of the monograph. Similarly, there is an intent to publish an IRA for PEG 40 Castor Oil monograph in PF 51(3) [May-Jun. 2025].
The above-mentioned activities are intended to strengthen the USP-NF standards for high-risk excipients while there is also an urgent need to detect DEG and EG in finished dosage forms. FDA’s laboratory has developed and validated a test method using Gas chromatography-Mass spectrometry (GC-MS) for determination of EG and DEG in cough, cold, and allergy products containing Glycerin.
In close collaboration with the FDA, USP intends to publish this method through the emerging standard approach for developing and sharing information with our stakeholders. The emerging standards are intended to increase transparency allowing for broader stakeholder participation by publishing on the USP website prior to formal notice and comment through publication in the Pharmacopeial Forum.
The intent is to post the method on the USP's Emerging Standards webpage around May 2025 to help analyze EG and DEG in finished drug dosage forms. USP welcomes stakeholders to evaluate this method and provide feedback.
USP also encourages stakeholders to submit their in-house EG and DEG testing methods for finished dosage forms. Similar to the recent PF proposal of general chapter, <470> Determination of Ethylene Glycol, Diethylene Glycol, and Triethylene Glycol in Polyethylene Glycol, a standalone general chapter may be considered for development to help global regulatory agencies address the EG and DEG contamination and adulteration in pharmaceutical products.
Should you have any questions, please contact Jenny Liu, Senior Principal Scientist (jyl@usp.org).