BRIEFING

 Vinorelbine Injection. This proposal is based on the version of the monograph official as of November 1, 2018. It is proposed to revise the monograph with the following changes:

1. Revise the Caution statement in the Definition for clarity.

2. Revise Identification A to move the retention time agreement into a new Identification B based on the Assay.

3. Revise the Assay as follows:

   • Revise the Detector to support Identification A.

   • Revise the Column to add particle size to the column dimensions.

   • Add the Run time.

   • Replace the retention time note in the System suitability section to present relative retention times as an aid in peak assignment.

   • Add a Tailing factor to the Suitability requirements.

   • Revise the requirement for the Relative standard deviation from NMT 2.0% to NMT 1.0% based on supporting data and to be consistent with the expectations of a modern chromatographic system.

   • Update molecular weights and include minor edits for clarity in the calculation of the Assay.

4. Revise the test for Organic Impurities as follows:

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

   • Revise the Chromatographic system section to reference the Assay.

   • Update the Samples in System suitability, and add a Note and Table 1 to the System suitability to present relative retention times as an aid in peak assignment and update the chemical information of epoxy vinorelbine and vinorelbine related compound A.

   • Revise the relative retention time of epoxy vinorelbine from 0.8 to 0.81.

   • Update Table 2 in the Acceptance criteria to list only the limits for specified degradation products, any unspecified degradation product, and total degradation products.

   • Include minor edits for clarity in the calculation of Organic Impurities.

   • 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”.

5. Replace the tests for Clarity of Solution and Color of Solution with the Container Content for Injections test in Specific Tests to strengthen the public standard.

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

7. In Sterility Tests, remove the reference to the membrane filtration technique to allow for flexibility.

8. In Other Requirements, replace the requirement from Injections and Implanted Drug Products 〈1〉 with the requirement from Labeling 〈7〉, Labels and Labeling for Injectable Products.

9. Add the Labeling section in Additional Requirements.

10. 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-465