Bioequivalence and Bioavailability Forum

Dear Kaushal!

❝ One BA/BE study was meeting acceptance criteria as per FDA retirement. (80-125%). IS this required to check outlier for pass bio-study?

See the 2001 guidance, VII. C. Outlier Considerations:

[…] deletion of outlier values is generally discouraged, particularly for nonreplicated designs.

Since deletion is discouraged, I would not expect FDA to ask for a check.

❝ Also if we apply outlier test for bio-study than one subject found as outlier and after excluding that subject, study goes to fail to meet acceptance criteria (80-125).

Now it gets interesting.
Not specifically an FDA issue, but regulators seems to be allergic to outlier testing. At the 3^rd EGA Symposium on Bioequivalence (London, June 2010) Gerald Beuerle presented an example where due to an obvious mix-up of samples between two subjects at C_max the study would pass with the “wrong” values and fail after exchanging them (or excluding both subjects as well). Even in this case (likely BE falsely concluded) members of EMA’s PK group defended their position against testing for outliers…
Nice for the sponsor but what about patient’s risk?