BRIEFING

 Sirolimus Tablets. Because there is no existing USP monograph for this drug product, a new monograph based on validated methods of analysis is proposed. On the basis of comments received, the proposal for this drug product which appeared in PF 47(1) [Jan.–Feb. 2021] was canceled and is replaced with a new proposal based on the following validated methods of analysis.

1. The liquid chromatographic procedures used in the Assay and Dissolution tests were validated using the Kromasil C18 brand of column with L1 packing. The typical retention times for sirolimus are about 4 min.

2. The liquid chromatographic procedure used in the test for Organic Impurities is based on analyses performed with the ACE C18 brand of column with L1 packing. The typical retention time for sirolimus is about 23 min. The acceptance criteria has been modified from the PF 47(1) proposal as follows:

   • Increased the reporting threshold from 0.04% to 0.1% to be consistent with International Council for Harmonisation recommendations.

   • Changed the term "Any unspecified impurity" to "Any unspecified degradation product".

   • Changed the term "Total impurities" to "Total degradation products".

   • Changed the name of Sirolimus-19-ene open ring to Secorapamycin, which is more commonly used. Sirolimus-19-ene open ring is still included as a footnote in Table 1 for additional clarity.

   • Widened the limit for Secorapamycin from NMT 1.0% to NMT 1.5% which is consistent with FDA-approved products.

3. Additional modifications from the PF 47(1) proposal include the following:

   • Changed Identification A from Ultraviolet-Visible Spectroscopy 〈197U〉 to UV spectra agreement as obtained in the Assay.

   • Updated the Packaging and Storage section.

   • Replaced USP Sirolimus RS with USP Sirolimus System Suitability Mixture RS to support the resolution requirement in the test for Organic Impurities.

 (SM1: M. Puderbaugh)

 Correspondence Number—C149742