BRIEFING

 Estradiol Vaginal Inserts. This proposal is based on the version of the monograph official prior to 2013. The following changes are proposed:

1. Replace the TLC-based Identification A with the UV spectral agreement of the estradiol peak of the Identification sample solution and Identification standard solution, as obtained in the Assay.

2. Revise the Assay as follows:

   • Remove the Note since this information is provided under the Standard solution and the Sample solution.

   • Revise the Chromatographic system to include the information for diode array detection needed to support the proposed Identification A.

   • Add the Identification standard solution and Identification sample solution to support Identification A.

   • Clarify the peak responses under the calculation.

3. Revise the Dissolution as follows:

   • Remove the pH range requirement for the Medium since this information is included under Dissolution 〈711〉.

   • Include the preparations for Standard solutions used to construct the calibration curve.

   • Clarify the use of Standard solution A and Standard solution C for the System suitability.

   • Update the calculation formula to be consistent with current USP style.

   • Add a column under Table 1 to include time points.

4. Revise the Organic Impurities test as follows:

   • Add Solution C which is used to prepare the Sample solution.

   • Update Table 2 to include the gradient and equilibration times. As a result, the Note under Table 2 is deleted.

   • Add a Sensitivity solution and a Signal-to-noise ratio system suitability requirement to align with User-Determined Reporting Thresholds 〈477〉.

   • Add Table 3 and a Note in the System suitability section to provide relative retention times for known impurities as an aid in peak assignment.

   • Update the table numbers in the Acceptance criteria as a result of the addition of Table 3.

   • Revise the tables in the Acceptance criteria section to list only the limits for specified impurities, any unspecified degradation product (where applicable), and total degradation products.

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

5. The references to Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉 are separated to more clearly communicate the requirements associated with each of the general chapters.

6. Revise the USP Reference Standards section to update and add chemical information for USP Estradiol Related Compound B RS, USP Estradiol Related Compound C RS, and USP Estrone RS.

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

 (SM5: H. Ramanathan)

 Case ID—SUB-1198