BRIEFING

 Neostigmine Methylsulfate. This proposal is based on the version of the monograph official as of May 1, 2020. It is proposed to revise the monograph with the following changes:

1. Revise the Chemical Information section as follows:

   • Add chemical structure of Neostigmine Methylsulfate.

   • Update the chemical name of Neostigmine Methylsulfate.

2. Revise Identification A to allow the flexibility of using either 197A or 197K.

3. Replace the colorimetry-based Identification B with the chromatographic retention time agreement as obtained in the proposed Assay.

4. The titration procedure in the Assay is replaced with a validated liquid chromatographic procedure, which is based on validation performed with the Kinetex C8 brand of column with L7 packing. The typical retention time for neostigmine is about 20 min.

5. Add an Organic Impurities test to strengthen the quality standard for this drug substance. The proposed liquid chromatographic procedure is similar to the proposed Assay.

6. Delete the nonspecific Melting Range or Temperature test because all the other tests in the monograph can adequately monitor the quality of the drug substance.

7. Add the Bacterial Endotoxins Test, the Sterility Tests, the Microbial Enumeration Tests, and a Labeling section to support preparation of sterile drug products.

8. Add the storage temperature in the Packaging and Storage section, to be consistent with manufacturer's storage conditions.

9. Add USP Neostigmine Related Compound A RS, USP Neostigmine Related Compound B RS, and USP Neostigmine Related Compound C RS to the USP Reference Standards section to support the proposed Assay and test for Organic Impurities.

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

 (SM4: D. Singh)

 Correspondence Number—C225253