Disturbing wording [Dissolution / BCS / IVIVC]

posted by ElMaestro  – Denmark, 2017-12-25 19:28 (2285 d 13:10 ago) – Posting: # 18081
Views: 5,466

Hi all,

re. FDA's new biowaiver guidance Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System:

I do absolutely not like this sentence on page 8 re. the calculation of f2:
"Two dissolution profiles are considered similar when the f2 value is ≥ 50. To allow the use of mean data, the coefficient of variation should not be more than (...)"

If taken verbatim this means that an f2-based method is not acceptable when the CV is high, full stop. In that case I believe there's just the Mahalanobis distance left as a semi-bad proposal for a way forward.
I think and hope they meant something like "Two dissolution profiles are considered similar when the f2 value is ≥ 50. To allow the use of the plain f2 as a measure of similarity of dissolution profiles, the coefficient of variation should not be more than (...)"
- this would keep the door open for bootstrapping which was what was done internally at FDA for the now slightly famous Mesalamine case.

Goodbye to bootstrapping or just a little snafu when they wrote the draft?

Pass or fail!
ElMaestro

Complete thread:

UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
119 visitors (0 registered, 119 guests [including 0 identified bots]).
Forum time: 08:38 CET (Europe/Vienna)

With four parameters I can fit an elephant,
and with five I can make him wiggle his trunk.    John von Neumann

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5