BRIEFING

 Vinorelbine Tartrate. 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 and chemical name of Vinorelbine Tartrate in the Chemical Information section.

2. Update the sample preparation procedure for 197K of Identification A to remove the requirement for a toxic solvent.

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

4. Revise the Assay as follows:

   • Add the Run time.

   • Replace the Note and add Table 1 reference to present relative retention times as an aid in peak assignment and update the chemical information of 3,6-Epoxy vinorelbine and Vinorelbine related compound A.

   • Revise the chemical name of 3,6-epoxy vinorelbine to epoxy vinorelbine.

   • Tighten the requirement for the Relative standard deviation from NMT 2.0% to NMT 0.73% based on supporting data and to be consistent with the expectations of a modern chromatographic system.

5. In the test for Organic Impurities:

   • Add the Sensitivity solution, revise the Standard solution, and update the Suitability requirements based on supporting data to be consistent with the expectations of modern chromatographic systems.

   • Update the relative retention time of epoxy vinorelbine from 0.8 to 0.81, and chemical information of 3,6-Epoxy vinorelbine and Vinorelbine related compound A in Table 1.

   • Revise Table 2 in the Acceptance criteria to list only the limits for specified impurities, any unspecified impurity, and total impurities.

   • Update the chemical names of impurities in Table 2.

   • In the Acceptance criteria, add 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”.

6. Replace the tests for Clarity of Solution and Color of Solution with Bacterial Endotoxins Test, Sterility Tests, and a Labeling section to support preparation of sterile drug products and to strengthen the monograph.

7. Update the pH test to provide clarity.

8. Update the chemical information of USP Vinorelbine Related Compound A RS in the USP Reference Standards section.

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

 (SM3: J. Kilari)

 Case ID—SUB-732; SUB-1519