EMA: No biowaivers for NTIDs [Dissolution / BCS / IVIVC]

posted by Helmut Homepage – Vienna, Austria, 2020-07-15 19:08 (428 d 20:24 ago) – Posting: # 21704
Views: 1,576

Hi dshah,

» We are working on a NTI drug with high variability for which different dissolution media is recommended by USFDA.
» For BE study as per USFDA- a fasting and fed study for highest strength is recommended.

Why don’t you simply tell us that the drug is rivaroxaban? :-D

» For EMA- A fed study on highest strength and a fasting study on another mid strength is concluded based on guideline.

Fine. Though there is no product-specific guidance for rivaroxaban publishd by the EMA, most people would consider it an NTID indeed. Following the logic of other NTID-guidances that would mean acceptance limits of 80.00–125.00% for Cmax and 90.00–111.11% for AUC. In rare cases the limits of Cmax have to narrowed as well. Up to you to provide a justification.

» For waiver request for other strength we need acceptable in vitro dissolution testing of all strengths.

Biowaivers for NTIDs are not acceptable. BE-Guideline APPENDIX III:

Applying for a BCS-based biowaiver is restricted to highly soluble drug substances with known human absorption and considered not to have a narrow therapeutic index.


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