BRIEFING

 〈469〉 Ethylene Glycol, Diethylene Glycol, and Triethylene Glycol in Ethoxylated Substances. This proposal is based on the version of the chapter official as of December 1, 2014. Concerns about ethylene glycol and diethylene glycol (EG and DEG) contamination in high-risk excipients used in drug products have been a serious public health issue since 1937. In response to a letter from the US FDA on February 10, 2023, two PF proposals were published to address this concern:

• In PF 50(5), a new general chapter, Determination of Ethylene Glycol, Diethylene Glycol, and Triethylene Glycol in Polyethylene Glycol 〈470〉, was proposed to address the potential risk of EG and DEG contamination in polyethylene glycol (PEG), and additional test procedures were described.

• In PF 51(3), it was proposed to revise the monograph for Polyethylene Glycol 40 Castor Oil to include a more user-friendly, validated EG and DEG test and move it to the Identification section. The revised Polyethylene Glycol 40 Castor Oil was published via Interim Revision Announcement with an official date of January 1, 2026.

In addition, we received multiple requests to revise the EG and DEG test in ethoxylated excipients. Therefore, on the basis of comments received and supporting data, it is proposed to make the following changes to 〈469〉:

1. Add Procedure 1B to include a gas chromatography method that employs more user-friendly conditions  based on a G16 column. This method will apply to Polyethylene Glycol 40 Castor Oil, Polyoxyl 35 Castor Oil, Polyethylene Glycol 40 Castor Oil, and Polyoxyl 15 Hydroxystearate. As more ethoxylated substances are validated using this newly developed method, additional monographs will be updated. In the case of Polyethylene Glycol 40 Castor Oil, Procedure 1B is suitable for the Identification test as per the FDA's request.

2. Revise the list of ethoxylated substances that were covered in the original method, now labeled Procedure 1A.

 Additionally, minor editorial changes have been made to update the chapter to current USP style.

 (EXCC: A. Chang)

 Case ID—SUB-2744