Bioequivalence and Bioavailability Forum

Dear All

For HVD drugs recently Canada regulatory has published a notice proposing to adopt an average bioequivalence approach to HVDP with expanding limits based on the within-subject variability of the reference product.

As per general guidance of Canada mixed model is recommended for conventional two way crossover design.

Please suggest Which Statistical model to be followed for highly variable drugs (Canada Regulatory)?

I recommends widening of CI approach as recommended by EU, but do the Statistical analysis needs to be done same way i.e calculate Reference variability with separate model with only reference data and then analyse data with GLM and also check for outliers for Reference variability?

Or we can calculate reference variability as well as 90% CI with Mixed model (As per FDA for replicate study) and widen the acceptance limits as per reference variability, if necessary?

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Edit: Category changed. [Helmut]