BRIEFING

 Chlordiazepoxide Hydrochloride and Clidinium Bromide Capsules. This proposal is based on the version of the monograph official as of November 5, 2021. It is proposed to make the following changes:

1. Add Identification B to be based on the UV spectra agreement of the major peaks of the Sample solution and Standard solution, as proposed in the Assay.

2. In the Assay:

   • Update the Sample solution preparation to provide flexibility and align with current practice.

   • Update the Detector to include the information to run Identification B.

   • Add the Column particle size based on laboratory data.

   • Add the Tailing factor to strengthen the public standard.

3. In Dissolution Test 1:

   • Update the Buffer preparation.

   • Update the Column dimensions.

4. In Dissolution Test 2, update the Sample solution preparation to provide flexibility and to align with current practice.

5. In the test for Organic Impurities:

   • Replace the thin-layer chromatography-based test for the Limit of Chlordiazepoxide Related Compound A and 2-Amino-5-Chlorobenzophenone with a liquid chromatographic procedure. The procedure was validated using an ACE 5 C18-PFP brand of column with L1 packing. The typical retention time for chlordiazepoxide is 42 min at 254 nm. The typical retention time for clidinium is 18 min at 210 nm.

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

6. Add the storage temperature in the Packaging and Storage section.

7. In the USP Reference Standards section:

   • Add the IUPAC name for USP Clidinium Bromide Related Compound A RS.

   • Add USP Trospium Chloride Related Compound A RS to support the updated test for Organic Impurities.

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

 (SM4: Y. Yang)

 Case ID—SUB-293