Two FDA Warning Letters: Identity Testing of Incoming Components

At the beginning of January, the U.S. Food and Drug Administration (FDA) has published two new Warning Letters to companies registered as a manufacturer of over-the-counter (OTC) drug products in the United States.

Warning Letter 320-24-13, dated 15 December 2023, was sent to a company in India and Warning Letter 320-24-14 dated 28 December 2023 to a manufacturer in South Korea.

In both cases, following a review of records provided by the companies upon FDA's request, the following CGMP violations are mentioned:

• "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)).
• Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a))."

The key point is that it could not be demonstrated that each shipment of each lot of the incoming components were tested at high-risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination. In particular, the identity testing for these 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.

Both firms were already placed an Import Alert 66-40 ("Detention Without Physical Examination of Drugs From Firms Which Have Not Met Drug GMPs").

In the Warning Letters, the FDA provides a list of measures that must be fulfilled and reported to the FDA, including the following:

• A commitment to provide DEG and EG test results.
• A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination.
• A comprehensive, independent review of the material system.
• A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer.

There have been numerous similar cases in recent months, also relating to the testing of DEG and EG. You can find examples in our news archive:

• Ethylene and Diethylene Glycol Testing again in Focus of FDA Warning Letters
• Series of FDA Warning Letters due to inadequate Testing of Glycerin and Other High-Risk Drug Components
• FDA Warning Letter to Indian Manufacturer: Glycerine used in Manufacturing not Tested according to USP