β = 1 – π [RSABE / ABEL]

posted by Helmut Homepage – Vienna, Austria, 2018-04-04 15:03 (1596 d 03:38 ago) – Posting: # 18640
Views: 6,238

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. :-D

» … 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 σwT/σwR 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

Does the conventional ABE (90% CI) pass these narrower limits?

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%?

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