BRIEFING

 Fluoxetine Oral Solution. This proposal is based on the version of the monograph official as of May 1, 2020. On the basis of comments received, the previous proposal that appeared in PF 46(5) [Sep.–Oct. 2020] was canceled and it is proposed to revise the monograph with the following changes:

1. Replace the IR spectral agreement test in Identification A with a test based on UV spectral agreement using the proposed Assay. This revision avoids the use of toxic solvents in the preparation of the sample.

2. Add Identification B based on retention time agreement using the proposed Assay to strengthen the monograph.

3. Replace the liquid chromatographic procedures in the Assay and the test for Organic Impurities with a procedure that is more specific. This procedure was validated using the XSelect CSH Fluoro-Phenyl brand of column with L43 packing. The typical retention time for fluoxetine is about 36 min.

4. In the Organic Impurities test, add the specified degradation products of fluoxetine and propose acceptance criteria for specified, unspecified, and total degradation products based on approved specifications.

5. In the Acceptance criteria of the Organic Impurities test, the numerical reporting threshold has been replaced with a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility. For more information about this change, please see the USP Compendial Notice "New Chapter 〈477〉 User-Determined Reporting Thresholds and its Implementation in USP–NF Monographs".

6. Add a storage requirement to the Packaging and Storage section for consistency with FDA-approved package inserts.

7. Revise the USP Reference Standards section to include USP Fluoxetine Related Compound A RS to support the proposed revisions throughout the monograph.

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

 Manufacturers are encouraged to submit their FDA-approved specifications to USP if they are different from those proposed.

 (SM4: S. Dragan)

 Case ID—SUB-600