FDA Global Supply Chain Concerns Prompt Glycerin DEG Testing Guidance

Pharmaceutical manufacturing facilities and compounding pharmacists should include tests for diethylene glycol content in the identity testing of all lots of glycerin they receive, according to an FDA guidance reflecting growing concern about vulnerabilities in the global supply chain.

Glycerin is widely used in OTC and personal care products such as lozenges and toothpastes, soaps and moisturizers. Brands made with the substance include Procter & Gamble's Crest toothpaste line, and it is an active ingredient in Fleet suppositories.

In the May 2 Federal Register, the agency said consistent DEG testing is needed because deaths from DEG poisoning have been reported as recently as October 2006 in Panama.

In 1996, FDA issued an import alert on bulk glycerin after acetaminophen elixir manufactured with DEG-contaminated glycerin poisoned and killed dozens of children in Haiti (¹ (Also see "In Brief: Import alert on bulk glycerin" - Pink Sheet, 5 Aug, 1996.), p. 34).

FDA said cases of DEG contamination from 1990 through 2006 were marked by similarities including manufacturers of the contaminated products relied on certificates of DEG analysis provided by glycerin suppliers and did not performing full identity testing on the glycerin raw material.

The agency said it found "no reason to believe that the U.S. supply of glycerin is affected at the present time," but "the serious nature of this potentially fatal problem and the global nature of the pharmaceutical supply chain" prompts it to emphasize testing for DEG.

FDA's Center for Drug Evaluation and Research pointed out the Food, Drug and Cosmetic Act was enacted in response to a U.S. outbreak of DEG poisoning in 1937, when 109 people died after ingesting elixir of sulfanilamide made with DEG as a solvent.

The agency issued this guidance as it deals with nationwide recalls of pet foods manufactured with melamine-contaminated wheat gluten imported from China. FDA and the Agriculture Department said April 30 they determined byproducts from the contaminated pet food have been used in chicken feed on some Indiana farms.

FDA issued the ² guidance as level 1 - for immediate implementation - and is not seeking comment prior because of the potential for a serious public health impact.

The glycerin testing guidance recommends drug product manufacturers perform a specific identity test in the United States Pharmacopeia monograph for glycerin, including a limit test for DEG, on all containers of glycerin before the substance is used in the manufacture or preparation of drug products.

The USP monograph set the relevant safety limit for DEG at 0.1 percent, according to the guidance.

Manufacturers also can use equivalent identification procedures with tests to detect and quantify DEG provided they meet the relevant safety limit, CDER's Office of Compliance said.

The guidance also recommended firms inform all staff in pharmaceutical manufacturing facilities, "especially personnel directly responsible for receipt, testing, and release of glycerin," of the importance of proper testing and the potential hazards if the testing is not done.

Additionally, the guidance advised manufacturers to know their supply chain for glycerin and for re-packers and other operations distributing and preparing glycerin to test the ingredient when it is intended for use in drug products.

Pharmacies using glycerin in compounding drug products should either test it for DEG content or ensure suppliers conduct proper testing, according to the guidance.

Similar to other FDA guidance documents, this guidance does not establish legally enforceable responsibilities but describes the agency's current thinking on the topic, FDA noted.

- Malcolm Spicer ([email protected])