## β = 1 – π [RSABE / ABEL]

Hi Jay,

» In any two way ABE study, if the 90%CI is not within the range of 80-125%, most of time the same is reflected in the T/R …

Well, the CI is constructed around the GMR.

» … and also the dissolution graphs.

Nope. Only if dissolution would be the rate-limiting step. Otherwise

» For NTID as per USFDAs GL below three criteria should be followed,

» - Upper 95% CI ≤0 (SABE)

» - 90% CI should be within 80-125%

» - UL of 90% CI for σWT/σWR should be ≤ 2.5 (ABE)

You are mixing something up. Actually:

- Upper 95% CI ≤0 (SABE)

- 90% CI should be within 80-125% (ABE)

- UL of 90% CI for σ

» As per the case mentioned in above post, the ISCV of test and ref is very low (around 6-7), T/R is near to 100 and also meeting BE criteria in ABE. So if only 95% CI in SABE does not meet criteria (0.0001) so how the reason for the difference between test and reference can be interpreted.

The FDA’s “implied BE limits” can be calculated by \(e^{\mp \log{(1.11111)}\cdot \sqrt{\log{(0.30^2+1)}}/0.1}\) which are in your case:

These three tests are not

Counterquestion: Did you ever succeed in convincing the FDA to accept a conventional BE study which showed a 90% CI of 79.99–125.01%?

» In any two way ABE study, if the 90%CI is not within the range of 80-125%, most of time the same is reflected in the T/R …

Well, the CI is constructed around the GMR.

_{}» … and also the dissolution graphs.

Nope. Only if dissolution would be the rate-limiting step. Otherwise

*in vitro*cannot (!) be predictive of*in vivo*. There a tons of studies with completely dissimilar dissolution profiles which passed BE easily.» For NTID as per USFDAs GL below three criteria should be followed,

» - Upper 95% CI ≤0 (SABE)

» - 90% CI should be within 80-125%

» - UL of 90% CI for σWT/σWR should be ≤ 2.5 (ABE)

You are mixing something up. Actually:

- Upper 95% CI ≤0 (SABE)

- 90% CI should be within 80-125% (ABE)

- UL of 90% CI for σ

_{wT}/σ_{wR}should be ≤ 2.5 (comparison of variabilities)» As per the case mentioned in above post, the ISCV of test and ref is very low (around 6-7), T/R is near to 100 and also meeting BE criteria in ABE. So if only 95% CI in SABE does not meet criteria (0.0001) so how the reason for the difference between test and reference can be interpreted.

The FDA’s “implied BE limits” can be calculated by \(e^{\mp \log{(1.11111)}\cdot \sqrt{\log{(0.30^2+1)}}/0.1}\) which are in your case:

`CV (%) BE-limits (%)`

6 93.88 106.52

7 92.90 107.64

These three tests are not

*directly*related. Fine if you pass the latter two. Bad luck if you fail the first by a small margin. How was the study powered? If you targeted a power of 80–90%, the chance of failing for a product which*is*BE would be 10–20%. Daily life. See John’s reply above.Counterquestion: Did you ever succeed in convincing the FDA to accept a conventional BE study which showed a 90% CI of 79.99–125.01%?

—

Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

Science Quotes

*Dif-tor heh smusma*🖖Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

Science Quotes

### Complete thread:

- FDA: RSABE for NTID Jay 2018-03-26 13:31 [RSABE / ABEL]
- FDA: RSABE for NTID jag009 2018-03-26 17:57
- FDA: RSABE for NTID Jay 2018-04-02 06:28
- FDA: RSABE for NTID pjs 2018-04-02 15:07
- FDA: RSABE for NTID Jay 2018-04-04 14:24
- β = 1 – πHelmut 2018-04-04 15:03
- Warfarin Sodium 95% Upper bound criteria Nirali 2019-01-30 15:38
- Upper bound in RSABE ≤0 Helmut 2019-02-02 14:15
- Upper bound in RSABE ≤0 Nirali 2019-02-12 07:10

- Upper bound in RSABE ≤0 Helmut 2019-02-02 14:15

- Warfarin Sodium 95% Upper bound criteria Nirali 2019-01-30 15:38

- β = 1 – πHelmut 2018-04-04 15:03

- FDA: RSABE for NTID Jay 2018-04-04 14:24

- FDA: RSABE for NTID pjs 2018-04-02 15:07

- FDA: RSABE for NTID Jay 2018-04-02 06:28

- FDA: RSABE for NTID jag009 2018-03-26 17:57