BRIEFING

 Busulfan Tablets. This proposal is based on the version of the monograph official prior to 2013. Based on comments received, the proposal in PF 45(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 the Definition as follows:

   • Change the Acceptance criteria from 93.0%–107.0% to 91.0%–105.0%, based on available FDA-approved specifications.

   • Add a Caution statement based on the safety requirements for handling busulfan.

2. Revise the Identification as follows:

   • Replace the use of a melting point in Identification A with the chromatographic retention time agreement using the proposed Assay.

   • Delete Identification B, Identification C, and Identification D as the tests are nonspecific.

3. Replace the titration procedure in the Assay with a gas chromatography (GC) procedure validated using the DB-5 brand of column with phase G27. The typical retention time for busulfan derivatized as 1,4-diiodobutane is about 3 min.

4. Delete the Disintegration test from the Performance Tests section.

5. Add the test for Organic Impurities. The ion chromatography (IC) procedure was validated using the Dionex Ion Pac AG4A-SC brand of guard column with L94 packing and the Dionex Ion Pac AS4A-SC brand of analytical column with L12 packing. The typical retention time for methanesulfonate is about 5 min.

6. Add a Specific Tests section with Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉.

7. Revise the Additional Requirements section as follows:

   • Add a storage condition to the Packaging and Storage section.

   • Add a USP Reference Standards section to include USP Busulfan RS and USP Potassium Methanesulfonate RS to support the revision to the Assay and the test for Organic Impurities.

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

 (SM3: A. Leeks, Jr)

 Case ID—SUB-1853, SUB-2404, SUB-2505