BRIEFING

 Gadodiamide Injection. This proposal is based on the version of the monograph official as of August 1, 2022. It is proposed to revise the monograph as follows:

1. Revise Identification A to include the requirement to compare the Sample solution with the Standard solution to be consistent with the sponsor's current procedure.

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

   • Add the Postcolumn reagent apparatus to include the reagent coil dimension information, which is critical to provide sufficient time for the postcolumn reaction and include a Flow rate for the Postcolumn reagent in the Chromatographic system.

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

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

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

   • Add a Sensitivity solution to allow the inclusion of the Signal-to-noise ratio as a System suitability requirement.

   • Revise the Resolution requirements.

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

   • Rename "impurity" as "degradation product" and rename "other individual impurity" as "unspecified degradation product" to be consistent with International Council for Harmonisation terminology.

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

4. Delete the Osmolality and Osmolarity test because this is a manufacturing process parameter and is not required for the public standard.

5. Replace the specific Bacterial Endotoxins Test acceptance criteria with "meets the requirements" to be consistent with the current USP practice

6. Add Particulate Matter in Injections, Sterility Tests, and Container Content for Injections requirements, which are necessary for parenteral dosage forms.

7. Delete the general Injections and Implanted Drug Products requirements because the revision adds all the important quality parameters for parenteral dosage forms separately.

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

 (SM4: R. Nguyen)

 Case ID—SUB-1221 and SUB-1679