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RegisterFDA prefer bootstrap f2 to MSD method [Dissolution / BCS / IVIVC]
Hi all,
I just found this interesting article yesterday written by Barbara Davit and other 3 FDA staff from Division of Bioequivalence II.
"Expectations of the US-FDA regarding dissolution data in generic drug regulatory submissions"
Most interesting part for me is the following phrases in the section "Dissolution profile comparison":
"...For circumstances where wide variability is observed, a statistical evaluation of f2 metric (an f2 confidence interval) can be calculated using a bootstrapping approach19.
According to the dissolution guidance, "Model Independent Multivariate Confidence Region Procedure" is suggested for comparison of dissolution profiles in instances where within batch variation is more than 15% CV20. Recent data from ANDA submissions lead the DB to believe that this method is likely to be less discriminating and sensitive than the f2 test. Therefore, the DB recommends the applicant use the f2 confidence interval approach when the mean data cannot be used for the f2 test as a result of high dissolution variability. ..."
Well, given that so many people were asking here about Mahalanobis calculation etc I guess this is an interesting turn of event. I'm no statistician but I'd say bootstrap f2 should be much easier than multivariate statistical distance method (or so I thought, see below)
Now comes my "hidden agenda"
I used to do f2 in M$ Excel with "eyeball" as to which data point should be included etc. for 1000 bootstrap dataset that's not an option. I'm currently struggling with SAS to apply the f2 criteria such as at least 3 point, no more than 1 point > 85% etc. It's much harder than I thought.
Any help here would be really appreciated.
Also, given that FDA's encouraging this method it would be nice to have R package/macro to do that. Any R-guru?
All the best
Shuanghe
I just found this interesting article yesterday written by Barbara Davit and other 3 FDA staff from Division of Bioequivalence II.
"Expectations of the US-FDA regarding dissolution data in generic drug regulatory submissions"
Most interesting part for me is the following phrases in the section "Dissolution profile comparison":
"...For circumstances where wide variability is observed, a statistical evaluation of f2 metric (an f2 confidence interval) can be calculated using a bootstrapping approach19.
According to the dissolution guidance, "Model Independent Multivariate Confidence Region Procedure" is suggested for comparison of dissolution profiles in instances where within batch variation is more than 15% CV20. Recent data from ANDA submissions lead the DB to believe that this method is likely to be less discriminating and sensitive than the f2 test. Therefore, the DB recommends the applicant use the f2 confidence interval approach when the mean data cannot be used for the f2 test as a result of high dissolution variability. ..."
Well, given that so many people were asking here about Mahalanobis calculation etc I guess this is an interesting turn of event. I'm no statistician but I'd say bootstrap f2 should be much easier than multivariate statistical distance method (or so I thought, see below)
Now comes my "hidden agenda"
I used to do f2 in M$ Excel with "eyeball" as to which data point should be included etc. for 1000 bootstrap dataset that's not an option. I'm currently struggling with SAS to apply the f2 criteria such as at least 3 point, no more than 1 point > 85% etc. It's much harder than I thought.
Any help here would be really appreciated. Also, given that FDA's encouraging this method it would be nice to have R package/macro to do that. Any R-guru?
All the best
Shuanghe
—
All the best,
Shuanghe
All the best,
Shuanghe
Complete thread:
- FDA prefer bootstrap f2 to MSD methodShuanghe 2013-06-14 10:55
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- bootstrap f2 in R d_labes 2013-06-14 13:48
- Off-topic Helmut 2013-06-14 14:30
- bootstrap f2 in R Shuanghe 2013-06-14 15:13
- bootstrap f2 in SAS d_labes 2013-06-14 15:55
- FDA prefer bootstrap f2 to MSD method yjlee168 2013-06-15 22:17
- "FDA acceptable" software or code to calculate bootstrap F2? sameep 2015-01-07 06:08
- FDA prefer bootstrap f2 to MSD method AngusMcLean 2013-06-18 16:06
- R-package for bootstrapping f2? d_labes 2013-06-19 08:20
- R-package for bootstrapping f2? AngusMcLean 2013-06-19 21:51
- Bootstrapping f2 in Pascal d_labes 2013-06-20 08:18
- source code is available? ElMaestro 2013-06-20 12:45
- Yes, source code is available yjlee168 2013-06-20 13:21
- Bootstrapping f2 in Pascal AngusMcLean 2013-06-20 15:29
- Bootstrapping f2 in Pascal AngusMcLean 2013-06-22 00:47
- source code is available? ElMaestro 2013-06-20 12:45
- Bootstrapping f2 in Pascal d_labes 2013-06-20 08:18
- R-package for bootstrapping f2? AngusMcLean 2013-06-19 21:51
- R-package for bootstrapping f2? d_labes 2013-06-19 08:20
- bootstrap f2 in R d_labes 2013-06-14 13:48
Ing. Helmut Schütz