BRIEFING

 Gadodiamide. 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 nonspecific Identification B with a test based on the retention time agreement as obtained in the Assay.

2. Revise the Assay to be consistent with the validated method as follows:

   • Revise the Mobile phase preparation.

   • Revise the Postcolumn reagent preparation.

   • Remove the redundant phrase "base-deactivated" from the description of the LC column, as the chromatographic column database includes the information as Supelcosil C18 DB.

   • Revise the Postcolumn reagent apparatus to include the reagent coil internal volume information, which is critical to provide sufficient time for the postcolumn reaction.

   • Revise the Column temperature from 20°–35° to 30°.

   • Add a Flow rate for the Postcolumn reagent.

   • Add a method Run time.

   • Revise the Relative standard deviation acceptance criteria from NMT 2.5% to NMT 1.1% in the Suitability requirements.

3. Delete the redundant Content of Gadolinium test because it is not needed for the public standard.

4. Revise the Limit of Free Gadolinium (III) test as follows:

   • Revise the test to be consistent with the validated method.

   • Add a General Chapter reference for Titrimetry 〈541〉 to the Titrimetric system for clarity.

   • Add an equation for the calculation.

5. Revise the Limit of Free Diethylenetriamine Pentaacetic Acid Bismethylamide test as follows:

   • Revise the test to be consistent with the validated method.

   • Add standardization instructions for the Gadolinium (III) solution.

   • Add a General Chapter reference for Titrimetry 〈541〉 to the Titrimetric system for clarity.

6. Revise the Limit of Methylamine test to be consistent with the validated method and the current USP practice as follows:

   • Add an Instrumental conditions section to be consistent with the current USP practice.

   • Include a storage temperature for the OPA reagent to be consistent with the validated method.

   • Clarify the Standard solution preparation as "Add 3.0 mL of the OPA reagent to 3.0 mL of each Standard solution".

   • Add an equation for the calculation.

   • Revise the Acceptance criteria to be on the anhydrous basis based on approved specifications.

7. Delete the Limit of Acetone, Ethyl Alcohol, and Isopropyl Alcohol test because residual solvents are covered by the General Notices.

8. Revise the Organic Impurities procedure to be consistent with the validated procedure as follows:

   • Revise the Mobile phase, Postcolumn reagent, and Chromatographic system. Use the same specified in the Assay.

   • Add relative retention time information to aid in peak assignment.

   • Revise the Resolution in the Suitability requirements based on the supporting data.

   • Delete the Relative standard deviation in the Suitability requirements because the calculations of impurities are based on the percentage of total area.

9. Replace the specific Bacterial Endotoxins Test acceptance criteria to be consistent with the current USP practice.

10. Delete the Tests for Specified Microorganisms because it is not relevant for all approved applications.

11. Revise the method specified in the Water Determination test from Method I to Method Ia for clarification.

12. Delete the Clarity of Solution test. The remaining tests are sufficient for the public standard.

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

 (SM4: R. Nguyen)

 Case ID—SUB-1220 and SUB-1678