Testing of Glycerin for Diethylene Glycol
The Office of Compliance in the Center for Drug Evaluation and Research (CDER) has released a Guidance for Industry concerning the “Testing of Glycerin for Diethylene Glycol."
In the guidance introduction, the Office of Compliance states:
“This guidance is intended to alert pharmaceutical manufacturers, pharmacy compounders, repackers and suppliers to the potential public health hazard of glycerin contaminated with diethylene glycol (DEG), a poison. FDA has received and continues to receive reports about fatal DEG poisoning of consumers who ingested medicinal syrups, such as cough syrup or acetaminophen syrup, that were manufactured with DEG-contaminated glycerin. This guidance provides recommendations that will help pharmaceutical manufacturers, repackers, and other suppliers of glycerin, and pharmacists who engage in drug compounding, avoid the use of glycerin that is contaminated with DEG and prevent incidents of DEG poisoning.”
The guidance states further; “To avoid the use of DEG contaminated glycerin…The Agency recommends that:
Drug product manufacturers perform a specific identity test that includes a limit test for DEG on all containers of all lots of glycerin before the glycerin is used in the manufacture or preparation of drug products because of the serious hazard associated with DEG contamination. The relevant safety limit for DEG is 0.1%, as recognized by the USP monograph for glycerin. The Agency recommends that a manufacturer perform the identity test, including the limit test for DEG, which appear in the USP monograph for glycerin. Alternatively, a manufacturer may use an equivalent identification procedure that includes a test to detect and quantify DEG provided it meets the relevant safety limit. One alternative procedure is a thin-layer chromatography (TLC) method published in the Journal of AOAC International.
This identification test is done in accordance with the CGMPs, which require that each lot of a component undergo testing to confirm its identity before use in drug product manufacturing (21 CFR 211.84(d)(1) requires that “[a]t least one test shall be conducted to verify the identity of each component of a drug product. Specific identity tests, if they exist, shall be used”). A specific identity test for glycerin is found the United States Pharmacopeia (USP) monograph. The USP monograph for glycerin provides a two-part identity test: test A using “Infrared Absorption” and test B using gas chromatography that references the “Limit of Diethylene Glycol and Related Compounds.” The infrared absorption test identifies glycerin and DEG, but does not distinguish between the two. Test B distinguishes glycerin from DEG.
Drug product manufacturers know their supply chain for glycerin (i.e., the manufacturer of the component and any subsequent distributors.))
All manufacturers take every opportunity to ensure proper testing of glycerin for DEG contamination. All personnel in pharmaceutical manufacturing facilities (especially personnel directly responsible for receipt, testing, and release of glycerin) should be made aware of the importance of proper testing and the potential hazards if the testing is not done.
Repackers, and other who distribute and prepare glycerin for use in drug products, test glycerin that is used, sold for use, or intended for use in drug products.
Pharmacies that use glycerin in compounding drug products either test the glycerin for DEG content or ensure that such testing was properly done by a reliable supplier."
If we may provide a copy of the complete Guidance or, if we may assist you in the testing and documentation of your company’s component glycerin, please contact a customer service representative at Geneva Laboratories.