BRIEFING

 Ciclopirox Olamine. This proposal is based on the version of the monograph official as of May 1, 2020. it is proposed to revise the monograph as follows:

1. Add 197A to Identification A to allow the flexibility of using either 197K or 197A.

2. Add Identification B which is based on the retention time agreement using the proposed Assay.

3. Replace the titrimetric Assay with a validated LC procedure. The proposed LC procedure was validated using the Zorbax SB-CN brand of column with L10 packing. The typical retention time for ciclopirox is about 11 min.

4. Revise the acceptance criteria range from NLT 97.5% and NMT 101.5% to NLT 98.0% and NMT 102.0% in the Definition and Assay to support the replacement of a non-specific titration with the proposed LC procedure.

5. Delete the titrimetric procedure for Monoethanolamine Content. The proposed Identification test and Assay are sufficient for the monograph.

6. Revise the test for Organic Impurities as follows:

   • Replace the Standard stock solution and the Standard solutions with new preparations that include USP Ciclopirox Related Compound C RS to accommodate the proposed calculation and reporting for the specified impurities.

   • Add the Sensitivity solution to support the proposed Suitability requirements.

   • Update the Samples used in the System suitability.

   • Replace the relative retention times statement with Table 1 and add a Note to the System suitability section to present relative retention times as an aid in peak assignment.

   • Replace the Tailing factor criterion with the Relative standard deviation and update the Signal-to-noise ratio criteria in the Suitability requirements.

   • Add calculation equations and corresponding definition lists for quantitating specified and unspecified impurities.

   • Add Table 2 and present ciclopirox related compound B and ciclopirox related compound C as specified impurities aligning with the sponsor's supporting data.

   • Delete the "disregard any peak..." statement and add a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility.

7. Add USP Ciclopirox Related Compound C RS to the USP Reference Standards section to accommodate the proposed revisions. Add chemical formula and molecular weight information for USP Ciclopirox Related Compound A RS and USP Ciclopirox Related Compound B RS to be consistent with current USP style.

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

 (SM1: R. Nguyen)

 Case ID—SUB-523