Bioequivalence and Bioavailability Forum

Dear all,

There're many talks on FDA's scaled BE approach here but I couldn't find the topic on subject to analyse/include in BE protocol. Here it goes:

I've been reviewing a BE report, TRTR/RTRT full replicate. In the protocol it says that subjects who complete at least 2 periods (1 test and 1 reference product) will be assayed. it make sense for 2x2 standard BE that product should be crossed at least once.

In addition, " (sth. about average approach...) Only subjects who have evaluable data from at least one evaluable period of Test product and both evaluable periods for Reference product will be included in the reference-scaled bioequivalence analyses...."

My question is: is this phrase correct?

According to the FDA's draft guidance on progesterone, in order to apply SABE, Swr should be >= 0.294 and this value is calculated solely from Reference product (Dij). So for those subjects who has only 2 periods, both reference, shouldn't they also be included in the analysis for the sake of Dij, hence the Swr, calculation? Theoretically, with or without those subject, Swr might be >= or < 0.294 so it might affect the applicability of SABE.

Of course, in the study report I've been reviewing there's no such subject but it would be nice to know your opinion for the studies in the future.

More general question is: how to treat the topic of "Subject to Analyse" in replicate (partial or full) BE study?

Thanks.

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Edit:

Just checked EMA's BE guideline and PK working party's QA. BE guideline requires crossing at least once so subject included should at least have 1 test and 1 reference and QA specified for replicate study Swr should calculated only with reference data (remove test data). So the above question applies to European BE study as well: in the protocl, should we specify to include subject who has only 2 periods of reference?

Shuanghe,

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Edit: Category changed. [Helmut]