BRIEFING

 Venlafaxine Hydrochloride. This proposal is based on the version of the monograph official as of May 1, 2020. The following changes are proposed:

1. Update the molecular weight for venlafaxine hydrochloride in the Chemical Information section to be consistent with the current IUPAC values.

2. Add a chemical name in the Chemical Information section to be consistent with the current IUPAC naming convention.

3. Update Identification A to add 197A to provide the flexibility of using either 197A or 197K.

4. Due to sublimation of the material, Loss on Drying is replaced with the Karl Fischer-based direct titration method as described in Water Determination 〈921〉, Method I, Method Ia.

5. Update the Definition from calculated on the dried basis to calculated on the anhydrous basis to align with the revised Water Determination test.

6. In the Assay:

   • Clarify the wording of the Run time in the Chromatographic system.

   • Update the Relative standard deviation requirement from NMT 2.0% to NMT 0.73% to be consistent with the expectations for modern chromatographic systems and supporting data.

   • Update the basis for the Acceptance criteria to align with the revised Definition.

7. In the test for Organic Impurities:

   • Replace the cross reference to the Assay for the preparation of the Buffer and Mobile phase with explicit preparation instructions of all solutions required for this test.

   • Clarify the wording of the Run time in the Chromatographic system.

   • Add a Sensitivity solution for the assessment of Signal-to-noise ratio in the Suitability requirements to align with the reporting threshold.

   • In the Acceptance criteria, add a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility. For more information about this change, please see the USP Compendial Notice "〈477〉 User-Determined Reporting Thresholds and its Implementation in USP–NF Monographs".

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

 The current standard lacks a test and specification capable of monitoring chiral purity. Manufacturers are encouraged to submit their FDA-approved specifications for the expert committee's consideration.

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

 (SM4: H. Ramanathan)

 Case ID—SUB-428