Bioequivalence and Bioavailability Forum

Dear Chirag,

❝ When the initial and repeat data of drug was compared, the difference observed was about +/- 30%. This was the case with 3 subjects out of more than 65 subjects

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❝ ISR passed with more than 95% acceptance criteria

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❝ Does this cause concern where the difference between initial and repeat analysis data is more than 30% and ISR is still meeting the acceptance criteria.

Some questions:

- in how many runs were the samples of these 3 subjects analysed initially ? How many runs for re-analysis ?

- was the difference always in the same direction for all samples for each subject ? If yes, it just looks like an accuracy issue (one run may be 15 % too high, the second 15 % too low).

- was the difference in the same direction for the 3 subjects ? Higher, or lower than the initial result ? If the difference was systematically in the same direction, with 3 independent runs, you may have an issue with stability (either of the parent analyte, or of a metabolite). Did you analyse your ISR runs only at the end of the study, or on an ongoing basis each time you had enough samples to re-analyse in a run ?

Regards
Ohlbe