BRIEFING

 Polyethylene Glycol. This proposal is based on the version of the monograph official as of February 1, 2020. In response to the letter from the US Food and Drug Administration (FDA) on February 10, 2023, the Complex Excipients Expert Committee is proposing to revise the monograph by including an Identification test for Limit of Ethylene Glycol and Diethylene Glycol (EG/DEG) for Polyethylene Glycol with a molecular weight ≤1000 to address the risk of EG/DEG contamination and adulteration. Other revisions are also included. Based on the feedback received from stakeholders on the General Announcement, the responses to the survey, and the FDA's input, the Complex Excipients Expert Committee proposes to revise the monograph through an accelerated revision process - Interim Revision Announcement to make the following changes:

1. Add Identification A, which uses infrared spectroscopy.

2. Add the new Limit of Ethylene Glycol and Diethylene Glycol test as Identification B for Polyethylene Glycol with a molecular weight ≤1000, as per the letter from the US Food and Drug Administration. This gas-chromatography method is the same as the validated method in Ethylene Glycol, Diethylene Glycol, and Triethylene Glycol in Ethoxylated Substances 〈469〉. Based on several in-house EG/DEG methods submitted by stakeholders, USP plans to utilize an iterative approach to develop a new general chapter to propose available EG/DEG test methods for stakeholders to evaluate the equivalency and interchangeability of these methods and use them as alternative methods, if suitable, according to USP General Notices 6.30. Alternative and Harmonized Methods and Procedures. Please also note that, in addition to the percent limits of EG and DEG in this monograph, drug products should meet the requirement of maximum daily intake for Ethylene Glycol (6.2 mg) according to ICH Q3C, Residual Solvents 〈467〉, and USP General Notices, 5.60.20. Residual Solvents in USP and NF Articles.

3. In the Impurities section, delete the original two tests for Limit of Ethylene Glycol and Diethylene Glycol using packed GC column and UV spectrometry for Polyethylene Glycol with a molecular weight of ≤1000. Add a new Limit of Ethylene Glycol and Diethylene Glycol test using gel permeation chromatography for Polyethylene Glycol with a molecular weight of >1000. To reduce the burden of stakeholders, this Limit of Ethylene Glycol and Diethylene Glycol test for Polyethylene Glycol with a molecular weight of >1000 is included in the Impurities section due to less risk of contamination and adulteration of solid grades.

4. Add the USP Reference Standards section to include the reference standards used in the Identification tests and Limit of Ethylene Glycol and Diethylene Glycol test.

5. Although the Polyethylene Glycol monograph is under the Pharmacopeial Discussion Group (PDG) for harmonization among European Pharmacopeia, Japanese Pharmacopeia, USP, and recently India Pharmacopeia, it has not reached to the harmonization consensus yet, so the above revisions are for the USP Polyethylene Glycol monograph only.

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

 The comment period for this revision ends on July 31, 2024. In the absence of any significant adverse comments, it is proposed to implement this revision via an Interim Revision Announcement with an official date of November 1, 2024.

 (SE: J. Liu)

 Case ID—SUB-586