Bioequivalence and Bioavailability Forum

Dear Ken,

Sorry for the delayed answer.

❝ If the repeat is for analytical reason, and the 2nd value is far apart from the initial value, how do we justify the acceptance of the 2nd value ? What are the analytical reasons that can be given ? QCs passed.

If you re-analyse the sample for an analytical reason, that's normally because you consider that the initial value is not reliable (e.g. variation in IS response). Having a difference between the initial and the repeat value is somewhat expected.

❝ How far the difference in value between repeat and initial value to justify for the third injection ?

Again, if the repeat analysis is for an analytical reason: if the first value is not reliable, why compare it to the second value ?

❝ If the repeat is for abnormal value, if we repeat in duplicate, which repeat should be taken, the 2rd or the 3nd repeat ?? is the purpose of 3rd repeat for confirmation ? Then, we should take the 2rd repeat as final value ?

Several possibilities have been described, with decision trees which depend on the difference between the 1st, 2nd and 3rd values. Again, there is nothing described in any guidelines. You may be able to find decision trees published somewhere. Sorry I don't have any reference to provide.

❝ Have you ever come across a scenario that the 3rd repeat is different from the 2rd repeat ? Again, what is the specification or criteria we need to set to accept the value ?

Yes, sure, it happens. That's part of the decision trees... You may get in a situation where the value is not reportable, if there is too much difference between the 3 results.

❝ How do we justify to inspector on this issue ?

Show the inspector your SOP... And if they're not happy with your decision tree, show them where it comes from.