Ethylene and Diethylene Glycol Testing again in Focus of FDA Warning Letters

In recent months, the awareness for the impurities diethylene glycol (DEG) and ethylene glycol (EG) in pharmaceutical products was increased due to several FDA Warning Letters. We have reported on different examples where manufacturers failed to conduct proper identity testing of glycerin and other high-risk components, as can be seen in our news archive:

• Series of FDA Warning Letters due to inadequate Testing of Glycerin and Other High-Risk Drug Components
• Identity Testing of Glycerin in Focus of an FDA Warning Letter

The United States Food and Drug Administration (FDA) has now published two more Warning Letters, which also deal with this issue.

Warning Letter to K. Boeun Pharmaceutical Co., Ltd.

Warning Letter 320-23-35, dated 14 August 2023 was published on 22 August 2023. It is about a manufacturer of over-the-counter (OTC) drug products. The authority has reviewed the records the company submitted in response to a request for records and other information.

The FDA writes that based on the records and information the company provided, it was not demonstrated that it "adequately tested each shipment of each lot of the incoming components at high-risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination. These include, but are not limited to, testing of glycerin and sorbitol solution [...] used in manufacturing drug products to determine their appropriate identity." In particular, identity testing including the limit test as described in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of DEG or EG was not performed.

The FDA also draws attention to the Quality Unit (QU), which "did not effectively exercise its responsibilities to oversee the quality of [the] drug manufacturing operations. Specifically, [the] QU did not adequately exercise its authority in the approval or rejection of components in [the] Materials System."

Warning Letter to International Laboratories Corp. Ltd.

The second case, Warning Letter 320-23-34, dated 08 August 2023, is very similar in content, partly even identical in wording. Although the component concerned is not named, it can be assumed that it is probably about the identity testing of glycerin.

ECA Webinar

In light of recent FDA Warning Letters, the ECA has decided to hold a GMP Webinar "Ethylene and Diethylene Glycol Testing", which will take place on Thursday, 16 November 2023 from 15.00 to 16.30 h CET.