BRIEFING

 Esomeprazole Magnesium Delayed-Release Capsules. This proposal is based on the version of the monograph official as of June 1, 2025. On the basis of comments received, the pellet weight was removed as it is formulation dependent and a nominal concentration was added to the Sample solution in the test for Organic Impurities. Additionally, it is proposed to revise the monograph with the following changes:

1. Revise the Definition to lowercase the drug name to signify it is the drug substance.

2. Revise Identification A as follows:

   • Revise the reagent name of the monobasic sodium phosphate monohydrate to monobasic sodium phosphate in the Buffer.

   • Revise the reagent name of the tribasic sodium phosphate dodecahydrate to tribasic sodium phosphate in the Diluent.

   • Revise the reagent dibasic sodium phosphate salt to sodium phosphate, dibasic, dihydrate salt in the Diluent based on original validation data.

   • Add a nominal concentration to the Sample stock solution and the Sample solution.

3. Revise the Assay as follows:

   • Replace the cross reference for the Diluent with a preparation.

   • Revise the reagent name of the tribasic sodium phosphate dodecahydrate to tribasic sodium phosphate in the Diluent.

   • Add a nominal concentration to the Sample stock solution and the Sample solution.

4. Revise the Dissolution tests as follows:

   • Replace the cross references for the Chromatographic system in the Buffer stage for Test 2 and Test 3 with specifications.

   • Revise the reagent name of 0.1 N hydrochloric acid VS to 0.1 N hydrochloric acid in the Medium for Test 1, Buffer stage medium for Test 4, Acid stage medium for Test 2, Test 3, and Test 4, and the Buffer stage medium for Test 3. Revise the reagent name of 2 N hydrochloric acid TS to 2 N hydrochloric acid in the Medium for Test 1, Buffer stage medium for Test 4, Buffer stage medium and Diluent for Test 2, and the Sample solution in the Buffer stage for Test 4. Revise the reagent name of 2 N sodium hydroxide TS to 2 N sodium hydroxide in the Medium for Test 1, Buffer stage medium for Test 4, Buffer stage medium and Diluent for Test 2, and in the Buffer stage for Test 4, the Sample solution, Solution A and Diluent. Revise the reagent name of 0.1 N sodium hydroxide VS to 0.1 N sodium hydroxide in Diluent 2 for Test 3. Revise the reagent name of 0.1 N hydrochloric acid VS to 1 N hydrochloric acid in the Buffer stage medium for Test 3. Revise the reagent name of 0.1 N sodium hydroxide VS to 1 N sodium hydroxide in the Buffer stage medium for Test 3.

   • In Test 2, replace the diluted ammonia reagent with 1.5 N ammonium hydroxide in Solution A based on original validation data.

   • In Test 2, replace the column equilibration step in the Mobile phase with a column equilibration step in Table 1, based on current USP style.

   • In Test 2, add volume to the Acid resistance stage calculation based on original validation data.

   • In Test 4, replace the reagent name of ethanol with alcohol in the Diluent for the Acid stage and the Standard stock solution for the Buffer stage.

   • In Test 4, replace the reagent dibasic sodium phosphate salt with sodium phosphate, dibasic, heptahydrate salt in the Buffer and Solution A based on original validation data.

   • In Test 4, add a number of moles conversion to the equation to correctly represent the number of moles of esomeprazole per esomeprazole magnesium and to correct the molecular weight of esomeprazole in the Analysis for the Acid resistance stage.

5. Revise the Organic Impurities test as follows:

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

   • Remove the cross reference for the Diluent.

   • Replace the reagent name of tribasic sodium phosphate dodecahydrate with tribasic sodium phosphate in the Diluent.

   • Add text to the Sample solution for discarding filtrate based on current USP practices.

   • Replace the relative retention time of 1.00 with 1.0 for omeprazole in Table 5 based on current USP practices.

   • Add a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility.

   • Replace the "any individual impurity" with "any degradation product" in the Analysis to align with ICH terminology for drug products.

6. Revise the USP Reference Standards section to correct the IUPAC name for USP Omeprazole Related Compound A RS.

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

 The comment period for this revision ends on May 31, 2026. In the absence of any significant adverse comments, it is proposed to implement this revision via an Interim Revision Announcement with an official date of November 1, 2026.

 (SM3: A. Leeks, Jr)

 Case ID—SUB-2041