BRIEFING

 Chlordiazepoxide Hydrochloride. This proposal is based on the version of the monograph official as of May 1, 2020. Based on comments received, the proposal in PF 44(5) 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 allow the flexibility of using either 197A or 197K.

2. Replace Identification C with a test for the counterion following Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride.

3. In the Assay:

   • Update the Standard solution and the Sample stock solution preparations for clarity.

   • Include the column particle size and add a Run time for consistency with modern expectations.

   • Remove the Column efficiency requirement. The remaining system suitability requirements are sufficient.

   • Update the Tailing factor from NMT 2.0 to 0.8–1.8 to align with Chromatography 〈621〉.

   • Revise the Relative standard deviation from NMT 2.0% to NMT 0.73% to be consistent with the expectations for modern chromatographic systems.

4. In the Organic Impurities test:

   • Replace the TLC test for chlordiazepoxide related compound A and 2-amino-5-chlorobenzophenone with a more specific LC procedure. The procedure was validated using the Nucleosil C18 brand of column with L1 packing. The typical retention time for chlordiazepoxide is about 5 min.

   • Update the Acceptance criteria on the basis of comments and submissions received. Manufacturers are encouraged to submit their FDA-approved specifications to USP if they are different from those proposed in this revision.

5. Remove the nonspecific test for Melting Range or Temperature as the other tests in the monograph can adequately monitor the quality of the drug substance.

6. Delete all references to sterility in this monograph because there are no injectable drug products marketed in the United States. These references are included in the sections for Sterility Tests 〈71〉, Bacterial Endotoxins Test 〈85〉, Other Requirements, and Labeling.

7. Add a storage temperature requirement to the Packaging and Storage section.

8. Update the chemical information in the USP Reference Standards section to be consistent with current chemical information.

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

 (SM4: Y. Yang)

 Case ID—SUB-1814