BRIEFING

 Cefpodoxime Proxetil. This proposal is based on the version of the monograph official as of August 1, 2024. On the basis of comments received, the proposal in PF 47(1) has been canceled and is being replaced with a new proposal. It is proposed to revise the monograph with the following changes:

1. Revise Identification A to include 197A and 197K to allow flexibility.

2. Replace the use of 197U in Identification B with the chromatographic retention time agreement using the proposed Assay.

3. Delete Identification C, as the test is nonspecific. The remaining Identification tests are sufficient.

4. In the Assay:

   • Provide the preparations of Solution A and Solution B.

   • Clarify the preparation of Solution C and Mobile phase. Provide the pH of Solution C and instructions for pH adjustment, if needed.

   • Revise the Standard stock solution and Sample stock solution to provide flexibility. Revise the Standard solution and Sample solution to remove the filtration step since these solutions are fully dissolved.

   • Add a Run time based on supporting data.

5. In the test for Organic Impurities:

   • Provide the preparations of Solution A and Solution B.

   • Clarify the preparation of Solution C and Mobile phase. Provide the pH of Solution C and instructions for pH adjustment, if needed.

   • Revise the Sample solution to provide flexibility.

   • Revise Table 1 to ensure the elution of late-eluting impurities and to have the Mobile phase re-equilibration between injections be at the end of the table, as per current USP Style.

   • Revise the impurities quantitation from area normalization to quantitation using an external standard, based on available validation data. Add a Standard stock solution and Standard solution at the unspecified impurities level, and revise the relative standard deviation suitability requirement to support the quantitation change.

   • Add a table and revise the Note in the System suitability section to present relative retention times as an aid in peak assignment. Revise the table in the Acceptance criteria section to list only the limits for specified impurities, any unspecified impurity, and total impurities.

   • Delete the retention times for cefpodoxime proxetil S-epimer and cefpodoxime proxetil R-epimer in the System suitability section because USP uses relative retention times for peak identification, and the new Table 2 provides sufficient retention information.

   • Provide the identification of three unidentified impurities based on information received from an FDA-approved manufacturer. Provide identification information and relative retention times for the additional identified impurities.

   • Delete the Column efficiency criterion in the Suitability requirements, as other criteria are sufficient to assess system suitability.

   • Delete the acceptance criterion for "any unspecified impurity with relative retention time >2.0", and add cefpodoxime proxetil N-isopropoxycarbamate analog-1 and cefpodoxime proxetil N-isopropoxycarbamate analog-2 acceptance criteria, based on information from an FDA-approved manufacturer. Manufacturers with different FDA-approved limits are encouraged to submit approved criteria to the Expert Committee for consideration.

   • Add an acceptance criterion for cefpodoxime based on information from an FDA-approved manufacturer.

   • Revise the acceptance criterion for cefpodoxime proxetil 3-ene analog from NMT 3.0% to NMT 2.5%, based on the highest FDA-approved acceptance criteria.

   • Revise the acceptance criterion for any unspecified impurity from NMT 0.5% to NMT 0.15%, as this is the highest FDA-approved acceptance criteria. FDA-approved manufacturers are encouraged to submit approved criterion to the Expert Committee for consideration.

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

 (SM1: S. Shane)

  Case ID—SUB-813