BRIEFING

 Roflumilast. This proposal is based on the version of the monograph official as of December 1, 2024. On the basis of comments received, it is proposed to revise the monograph with the following changes:

1. In the Assay, delete the reference to 6 replicate injections in the Relative standard deviation as this is covered in Chromatography 〈621〉.

2. In Organic Impurities, Procedure 1:

   • Delete the re-equilibration note and revise Table 2 to add a re-equilibration step.

   • Update the Sensitivity solution to align with the Sample solution concentration.

   • Revise Table 3 and update the note in the System suitability section to present relative retention times as an aid in peak assignment.

   • Add Table 4 in the Acceptance criteria to list only the limits for specified impurities, any unspecified impurity, total specified impurities, total unspecified impurities, and total impurities.

   • Update the reporting threshold to the current format.

3. Add Organic Impurities, Procedure 2 to accommodate different impurity profiles. The analysis was performed with the Ascentis Express C18 brand of column with L1 packing. The typical retention time for roflumilast is about 32 min.

4. Add the Limit of Roflumilast Related Compound C test to accommodate different impurity profiles. The analysis was performed with ACE C18-PFP brand of column with L1 packing. The typical retention time for roflumilast related compound C is about 3 min.

5. Add a Labeling section to accommodate different impurity tests.

6. In the USP Reference Standards section, add USP Roflumilast Related Compound F RS and USP Roflumilast Related Compound G RS to support the proposed test for Organic Impurities, Procedure 2.

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

 (SM5: S. Cusick, N. Myers)

 Case ID—SUB-772