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

posted by Helmut Homepage – Vienna, Austria, 2020-07-15 19:08 (233 d 11:52 ago) – Posting: # 21704
Views: 1,023

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.

Dif-tor heh smusma 🖖
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

 Admin contact
21,370 posts in 4,463 threads, 1,495 registered users;
online 2 (0 registered, 2 guests [including 2 identified bots]).
Forum time: Saturday 06:00 CET (Europe/Vienna)

If debugging is the process of removing bugs,
then programming must be the process of putting them in.    Edsger W. Dijkstra

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz