BRIEFING

 Gadoteridol Injection. This proposal is based on the version of the monograph official as of May 1, 2020. It is proposed to revise the monograph as follows:

1. Revise the Definition to remove the redundant intended use because it is stated already in the Labeling section.

2. In Identification A, revise the Sample solution to provide clarity.

3. Revise the Assay in response to comments received and associated supporting data as follows:

   1. Include a pH adjustment in the Buffer preparation.

   2. Add a Run time requirement.

   3. Delete the Resolution requirement in Suitability requirements because of the potential absence of detectable levels of the gadoteridol isomer in the Standard solution.

   4. Add a Tailing factor requirement in the Suitability requirements to be consistent with the validated method.

   5. Revise the calculation equation to be consistent with the current format.

4. Revise the Limit of Gadoteridol Related Compound A test in response to the comments received and associated supporting data as follows:

   1. Revise the solution preparations and add solution storage temperature requirements of "Store between 2° and 8°" as appropriate.

   2. Add a Sensitivity solution and Blank preparation.

   3. Update the inner diameter and add the particle size of the column.

   4. Add a Run time requirement.

   5. Revise the System suitability requirements by adding requirements for the Tailing factor and Signal-to-noise ratio and by widening the Relative standard deviation requirement from NMT 2.0% to NMT 5.0%.

   6. Revise the calculation equation to include Blank corrections for peak responses.

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

   1. Revise the solution preparations as appropriate.

   2. Add a statement to clarify that the analytical solution concentrations are described on the anhydrous basis.

   3. Add a Sensitivity solution and Signal-to-noise ratio requirement.

   4. Add an autosampler temperature requirement.

   5. Add a Run time requirement.

   6. Revise the System suitability requirement by adding requirements for the Tailing factor and Signal-to-noise ratio.

   7. Revise the calculation equations.

6. Replace the Other Requirements, which cross references to Injections and Implanted Drug Products 〈1〉, with direct references to Sterility Tests and the test for Container Content For Injections 〈697〉.

7. Revise the Bacterial Endotoxins Test criteria from "8.3 EU/mL of Gadoteridol Injection" to "Meets the requirements" to be consistent with the current USP policy.

8. Revise Packaging and Storage requirements to be consistent with the approved package insert.

9. Revise the Labeling to be consistent with the approved package insert.

10. Update the chemical information presented in the USP Reference Standards section.

 Additional changes have been made to update the monograph to current USP style.

 (SM4: R. Nguyen)

 Case ID—SUB-822