Thursday, 16 November 2023 15.00 - 16.30 h
Just recently, we reported on a Warning Letter dated 18 July 2023 regarding a manufacturer who failed to conduct proper identity testing of glycerin and other high-risk components.
The United States Food and Drug Administration (FDA) has now published a whole series of Warning Letters, all dated 03 August 2023, that revolve around the same topic.
The main deficiency is as follows: "Your firm failed to conduct at least one test to verify the identity of each component of a drug product (21 CFR 211.84(d)(1))." According to 21 CFR 211.84(d)(1), "at 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."
The first example is about a company registered as a manufacturer of over-the-counter (OTC) drug products, which manufactures hand sanitizer, and topical products. In the Warning Letter (320-23-21), the authority writes - based on a review of record submitted upon FDA's request - that the company did not adequately test each shipment of each lot of the incoming components at high-risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination. This concerns in particular glycerin.
The FDA goes on, stating: "Identity testing for glycerin and certain other high-risk drug components include a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of DEG or EG. Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of this component for use in the manufacture of your drug products. The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide."
The FDA now expects, beside others measures, a commitment to provide DEG and EG test results, a risk assessment, and a comprehensive, independent review of the material system.
In this case (Warning Letter 320-23-30), the company manufactures OTC drug products, including toothpaste for children. The FDA writes that "ingredients of the drugs registered as manufactured at [the] firm include ingredients susceptible to Diethylene Glycol (DEG) and Ethylene Glycol (EG) substitution."
A request for records and other information send to the contact e-mail address provided in the registration file went unanswered, and an attempted to contact the company by telephone also failed. A follow-up written request was not responded.
The Warning Letter has now been issued because the FDA was not able to confirm compliance with CGMP and other applicable requirements. The FDA also placed all drugs and drug products manufactured by the firm on Import Alert.
The company in question manufactures several OTC drug products, including mouth wash. Following a review of records, the FDA writes in Warning Letter 320-23-24: "Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities [DEG or EG], you failed to assure the acceptability of these components for use in manufacture of your drug products."
The list of measures requested by the FDA is similar to those requested in the Warning Letter to Avaria Health & Beauty Corp.
The company to which Warning Letter 320-23-29 is addressed, manufactures OTC drug products, including sunscreen. Again, based on the records, it was not ensured that the firm adequately tested each shipment of each lot of the incoming components at high-risk of DEG or EG contamination.
As with the other Warning Letters, the FDA also explicitly points out the responsibility of the quality unit (QU). The FDA concludes that the QU "did not effectively exercise its responsibilities to oversee the quality of [the] drug manufacturing operations."
Warning Letter 320-23-26 was sent to an Indian OTC manufacturer, whose product list includes toothpaste for children and hand sanitizer. In this case, glycerin, propylene glycol, and sorbitol solution were probably not adequately tested for possible DEG or EG contamination.
The last example, Warning Letter 320-23-25, is once again based on a review of records. The company is a manufacturer of several drug products for children. In this case, the component concerned is not named. From the context, however, it can be assumed that it is probably about the identity testing of glycerin.