BRIEFING

 Ciclopirox. 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 98.0% and NMT 101.0% to NLT 98.0% and NMT 102.0% in the Definition and Assay to support the replacement of the non-specific titration with the proposed LC procedure.

5. 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.

6. 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-298