BRIEFING

 Cisatracurium Besylate. This proposal is based on the version of the monograph official as of May 1, 2020. It is proposed to revise the monograph with the following changes:

1. Update the molecular weight of Cisatracurium Besylate in the Chemical Information section.

2. Revise Identification A to allow the flexibility of using either 197A or 197K.

3. Replace the LC procedure in the Assay with a validated LC procedure sharing the same Chromatographic system as in the proposed Organic Impurities procedure.

4. Revise the test for Organic Impurities as follows:

   • Replace the existing LC procedure with a new LC procedure validated using the Kromasil 100-5-C18 brand of column with L1 packing. The typical retention time for cisatracurium is about 27 min.

   • Add a table and note in the System suitability to present Relative retention times as an aid in peak assignment.

   • Revise the table in the Acceptance criteria to list only the limits for specified impurities, any unspecified impurity, and total impurities.

   • Revise the limits for specified impurities based on supporting data from an approved manufacturer.

   • Propose a tightened acceptance criterion for any unspecified impurity based on supporting data from an approved manufacturer and to be consistent with the identification threshold in the International Council for Harmonisation Q3A guideline for drug substances having a maximum daily dose of ≤2 g.

   • Replace the disregard statement in the Acceptance criteria with a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility. For more information about this change, please see the USP Compendial Notice “New Chapter 〈477〉 User-Determined Reporting Thresholds and its Implementation in USP−NF Monographs″.

5. Specify the use of peak height in calculating Relative standard deviation, and add a note to present Relative retention times in the test for Limit of Methyl Besylate.

6. Add the Bacterial Endotoxins Test, Microbial Enumeration Tests, Tests for Specified Microorganisms, Sterility Tests, and a Labeling section to support preparation of sterile drug products.

7. Delete USP Cisatracurium Besylate System Suitability Mixture RS from the USP Reference Standards section based on the proposed Assay and Organic Impurities procedures.

8. Add USP Cisatracurium Related Compound H RS to the USP Reference Standards section to support the proposed Assay and Organic Impurities procedures.

9. Add USP Methyl Besylate RS to the USP Reference Standards section to support the Limit of Methyl Besylate test.

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

 (SM4: D. Singh)

 Correspondence Number—C150037; C173834