BRIEFING

 Cisatracurium Besylate Injection. 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. Replace the IR spectral agreement test in Identification A with a test based on UV spectral agreement using the proposed Assay. This revision avoids the use of toxic solvents in the preparation of the sample.

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

3. 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 degradation products, any unspecified degradation product, and total degradation products.

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

   • 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″.

4. Replace the use of the numerical acceptance limit with "Meets the requirements" in the Bacterial Endotoxins Test to align with the general chapter.

5. Delete the Other Requirements section as the reference to Injections and Implanted Drug Products 〈1〉 is not necessary, and add Particulate Matter in Injections and Container Content for Injections to the Specific Tests section based on FDA-approved specifications.

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

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

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

 (SM4: D. Singh)

 Correspondence Number—C154071; C155005