Posting Date: 26-Jan-2024
Expert Committee: Excipients Test Methods (ETM)
Input Deadline: 29-Feb-2024
Proposed New Title: <470> Determination of Ethylene Glycol and Diethylene Glycol in Polyethylene Glycol
Suggested audience: pharmaceutical industry and excipient manufacturers, users and distributors, academia, QA/QC specialists, formulators, regulatory, and regulatory agencies.
Estimated proposal PF: Pharmacopeial Forum 50(5) [Sep.–Oct. 2024]
Background and objectives: Consistent with a request in the FDA’s letter on February 10th, 2023, the Complex Excipients Expert Committee (CE EC) intends to propose revisions to the USP Polyethylene Glycol (PEG) monograph by including a Limit of Ethylene Glycol and Diethylene Glycol (EG/DEG) test in the Identification (ID) section to address the risk of EG/DEG contamination in PEG, especially liquid and semi-solid forms.
For liquid and semi-solid PEGs (MW ≤ 1000), the current USP General Chapter <469> Ethylene Glycol, Diethylene Glycol, and Triethylene Glycol in Ethoxylated Substances has a validated gas-chromatography (GC) testing procedure that is suitable for impurity analysis of EG/DEG. Chapter <469> is a stand-alone general chapter which stakeholders may use prior to methods being added to related official monographs.
Using the same stand-alone GC iterative approach as <469>, USP is working on developing a test method general chapter <470> for EG/DEG test in different PEGs, especially for PEG MW ≤ 1000. USP published a General Announcement on September 29, 2023, and conducted a survey regarding the DEG/EG determination in PEGs. In addition to other useful information, several stakeholders also provided USP with in-house validated EG/DEG testing methods for PEGs, which may be included in this new test method general chapter <470> under development.
Description of scope and application: Based on the feedback from stakeholders and the survey results, the CE EC and the Excipient Test methods ETM EC intends to propose to utilize a stepwise approach by including the existing DEG/EG test method in <469> in the ID section of the PEG monograph using an accelerated revision process with a 3-month public comment period as step one. Subsequently, the ETM EC plans to introduce other available EG/DEG test methods for PEGs in a new test method general chapter <470> under development, as step two, for stakeholders to evaluate the equivalency and interchangeability of these methods and use them as alternative methods in accordance with USP General Notices 6.30. Alternative and Harmonized Methods and Procedures as necessary.
Preliminary outline: The following represent the sections intended for the proposed General Chapter:
- Introduction
- Procedures:
- USP is currently evaluating several testing procedures for inclusion in the GC. Each testing procedure includes the following:
- Solutions preparation (including standard and sample solutions)
- Instrumental system
- System suitability requirements
- Analysis
- USP is currently evaluating several testing procedures for inclusion in the GC. Each testing procedure includes the following:
Anticipated activities: USP is requesting early input from stakeholders on this proposal of a new General Chapter <470> Determination of Diethylene Glycol and Ethylene Glycol in Polyethylene Glycol which is planned to be published for comments in Pharmacopeial Forum.
Contact: Tong (Jenny) Liu, Ph.D., Principal Scientist, at (240)221-2072, jyl@usp.org