1H-Pyrazolo[3,4-c]pyridine-3-carboxamide,4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl];
1-(4-Methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide [503612-47-3]
BRIEFING
Apixaban. This proposal is based on the version of the monograph to be official on December 1, 2026. On the basis of comments received, it is being proposed to add the Organic Impurities, Procedure 2 test to accommodate FDA-approved products with a different specification. The liquid chromatographic procedure was validated using the XBridge BEH Shield RP18 brand of column with L1 packing. The typical retention time for apixaban is about 5 min. Additionally, it is proposed to revise the monograph with the following changes:
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Widen the acceptance criterion for the Residue on Ignition test to NMT 0.15% to be consistent with FDA-approved specifications.
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In the Organic Impurities, Procedure 1 test, replace the reporting threshold limit in the Acceptance criteria with a reference to User-Determined Reporting Thresholds 〈477〉 to provide flexibility.
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Remove the test for Limit of Apixaban Related Compound H, Apixaban Related Compound G, and Apixaban Related Compound F based on supporting data to accommodate FDA-approved specifications. USP is currently developing a strategy for the control of mutagenic and potentially mutagenic impurities in compendial articles. An alternative approach for evaluating these impurities may be proposed in the future, as appropriate.
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Add a Labeling section to reflect the addition of the Organic Impurities, Procedure 2 test.
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In the USP Reference Standards section, remove USP Apixaban Related Compound F RS, USP Apixaban Related Compound G RS, and USP Apixaban Related Compound H RS because the test for Limit of Apixaban Related Compound H, Apixaban Related Compound G, and Apixaban Related Compound F is removed.
Additionally, minor editorial changes have been made to update the monograph to current USP style.
The comment period for this revision ends on January 31, 2027. In the absence of any significant adverse comments, it is proposed to implement this revision via an Interim Revision Announcement with an official date of July 1, 2027.
(SM6: F. Gu)
Case ID—SUB-2850