Bioequivalence and Bioavailability Forum

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?