Log in
RegisterDisturbing wording [Dissolution / BCS / IVIVC]
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?
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
Pass or fail!
ElMaestro
Complete thread:
- Disturbing wordingElMaestro 2017-12-25 18:28 [Dissolution / BCS / IVIVC]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Disturbing wording Helmut 2017-12-26 13:14
- Literature reported Permeability Studies Accepted? sameep 2017-12-28 11:10
- Reliable source, sufficient number of subjects Helmut 2017-12-28 12:17
- Comparative BA study vs Biowaiver for BCS I sameep 2018-01-02 09:35
- Reliable source, sufficient number of subjects Helmut 2017-12-28 12:17
- Literature reported Permeability Studies Accepted? sameep 2017-12-28 11:10
- Disturbing wording Helmut 2017-12-26 13:14
Ing. Helmut Schütz