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RegisterSABE or Normal BE? [RSABE / ABEL]
Dear All
Recently US FDA has published a Draft Guidance on Tacrolimus Capsule bioequivalence where it has suggested following
Type of study: Fasting and Fed
Design: Single-dose, 4-way, fully replicated crossover design in-vivo
Strength: 5 mg
Subjects: Healthy males and nonpregnant females, general population.
Additional Comments: Applicants may consider using the reference-scaled average bioequivalence approach for tacrolimus.
For details about Method for Statistical Analysis Using the Reference-Scaled Average Bioequivalence Approach for narrow therapeutic index drugs,sposnors are suggested to refer to recently published draft Guidance on Warfarin Sodium.
It says that
The study should be a fully replicated crossover design in order to
• Scale bioequivalence limits to the variability of the reference product; and
• Compare test and reference product within-subject variability.
Later on I found something which left me drooling
On page 3, step 3 it was written as
Use the unscaled average bioequivalence procedure to determine BE for individual PK parameter(s). Every study should pass the scaled average bioequivalence limits and also regular unscaled bioequivalence limits of 80.00-125.00%
Now questions are
a) Now in view of these lines, does a full replicate study is really going to help any sponsor in getting widening or still need to follow 80-125?
b) Cmax and AUC of Tacrolimus are not highly variable (Cmax~20% and AUC~16% observed in one full replicate study done at our end) then what is the need of using SABE?
Recently US FDA has published a Draft Guidance on Tacrolimus Capsule bioequivalence where it has suggested following
Type of study: Fasting and Fed
Design: Single-dose, 4-way, fully replicated crossover design in-vivo
Strength: 5 mg
Subjects: Healthy males and nonpregnant females, general population.
Additional Comments: Applicants may consider using the reference-scaled average bioequivalence approach for tacrolimus.
For details about Method for Statistical Analysis Using the Reference-Scaled Average Bioequivalence Approach for narrow therapeutic index drugs,sposnors are suggested to refer to recently published draft Guidance on Warfarin Sodium.
It says that
The study should be a fully replicated crossover design in order to
• Scale bioequivalence limits to the variability of the reference product; and
• Compare test and reference product within-subject variability.
Later on I found something which left me drooling
On page 3, step 3 it was written as
Use the unscaled average bioequivalence procedure to determine BE for individual PK parameter(s). Every study should pass the scaled average bioequivalence limits and also regular unscaled bioequivalence limits of 80.00-125.00%
Now questions are
a) Now in view of these lines, does a full replicate study is really going to help any sponsor in getting widening or still need to follow 80-125?
b) Cmax and AUC of Tacrolimus are not highly variable (Cmax~20% and AUC~16% observed in one full replicate study done at our end) then what is the need of using SABE?
—
~A happy Soul~
~A happy Soul~
Complete thread:
- SABE or Normal BE?luvblooms 2013-02-19 05:07 [RSABE / ABEL]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- FDA: rSABE for NTIDs Helmut 2013-02-19 11:05
- SABE or Normal BE? jag009 2013-02-19 15:23
- Sample size? Helmut 2013-02-19 17:25
- SABE or Normal BE? luvblooms 2013-02-20 05:26
- SABE or Normal BE? jag009 2013-02-20 15:20
- SABE or Normal BE? Helmut 2013-02-20 15:45
- SABE or Normal BE? ElMaestro 2013-02-20 16:08
- SABE or Normal BE? jag009 2013-02-21 17:10
- FDA’s example data sets Helmut 2013-02-21 17:18
- FDA’s example data sets jag009 2013-02-21 20:14
- FDA’s example data sets Helmut 2013-02-21 22:42
- FDA’s example data sets jag009 2013-02-22 15:46
- FDA’s example data sets Helmut 2013-02-22 16:33
- FDA’s example data sets jag009 2013-02-22 15:46
- FDA’s example data sets Helmut 2013-02-21 22:42
- FDA’s example data sets jag009 2013-02-21 20:14
- FDA’s example data sets Helmut 2013-02-21 17:18
- SABE or Normal BE? jag009 2013-02-21 17:10
- SABE or Normal BE? ElMaestro 2013-02-20 16:08
Ing. Helmut Schütz