BRIEFING

 Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets. This proposal is based on the version of the monograph official as of November 1, 2023. It is proposed to replace decarboxylated degradant with USP Fexofenadine Related Compound C RS in the Assay, Procedure 1, Assay, Procedure 2, and in the test for Organic Impurities, Procedure 1. The following changes to the monograph are also proposed:

1. Revise Identification A to clarify that "major" peaks refers to fexofenadine and pseudoephedrine.

2. Revise Identification B to provide target concentrations of fexofenadine hydrochloride and pseudoephedrine hydrochloride in the Sample solution.

3. Replace ephedrone with methcathinone in Assay, Procedure 1, Assay, Procedure 2 and in the tests for Organic Impurities, Procedure 1, Organic Impurities, Procedure 3, and Organic Impurities, Procedure 4.

4. Correct the relative retention time for fexofenadine related compound C in Assay, Procedure 1 and in the test for Organic Impurities, Procedure 1.

5. Replace the System suitability solution with the Standard solution for determination of Relative standard deviation in Assay, Procedure 1 and Assay, Procedure 2.

6. Add a Note to the System suitability section in Assay, Procedure 2 to provide relative retention times.

7. Add a Sensitivity solution and a Signal-to-noise ratio requirement in the test for Organic Impurities, Procedure 1.

8. Replace tertiary dehydrated impurity with fexofenadine olefin in the tests for Organic Impurities, Procedure 1 and Organic Impurities, Procedure 2.

9. Add a reporting threshold based on the maximum daily dose of the drug product in the tests for Organic Impurities, Procedure 1, Organic Impurities, Procedure 2, Organic Impurities, Procedure 3, and Organic Impurities, Procedure 4.

10. Revise the concentration of the Sensitivity solution to align with the 0.1% expected reporting threshold in the tests for Organic Impurities, Procedure 2 and Organic Impurities, Procedure 3.

11. Revise the Sample solution preparation in the tests for Organic Impurities, Procedure 2, Organic Impurities, Procedure 3, and Organic Impurities, Procedure 4 to accommodate both the 12 and 24 h strengths of the drug product.

12. Replace "impurity" with "degradation product" to align with International Council for Harmonisation Q3B terminology in the tests for Organic Impurities, Procedure 1, Organic Impurities, Procedure 2, Organic Impurities, Procedure 3, and Organic Impurities, Procedure 4.

13. Revise the acceptance criteria for any unspecified degradation product in the test for Organic Impurities, Procedure 4 to be consistent with International Council for Harmonisation Q3B.

14. Add a table and Note to the System suitability section within the tests for Organic Impurities, Procedure 1, Organic Impurities, Procedure 2, and Organic Impurities, Procedure 4 to present relative retention times as an aid in peak assignment and add chemical information for methcathinone and fexofenadine related compound B.

15. Revise the table in the Acceptance criteria section within the tests for Organic Impurities, Procedure 1, Organic Impurities, Procedure 2, and Organic Impurities, Procedure 4 to list only the limits for specified degradation products, any unspecified degradation product, and total degradation products.

16. Update the USP Reference Standards section to include USP Fexofenadine Related Compound C RS.

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

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

 (SM5: M. Koleck)

 Correspondence Number—C325516