Bioequivalence and Bioavailability Forum

Dear all,

just found FDA’s first official statement about acceptance of Reference Scaled Average Bio­equi­va­lence in the drafted product-specific guideline from Oct 2008.

Quote from the document:

Available data indicate that this product may be highly variable in the bioequivalence parameters AUC and/or C_max. You may consider conducting bioequivalence studies using a replicate design approach. These replicate design studies may be analyzed using the reference scaled approach. The reference-scaled approach adjusts the bioequivalence limits of highly variable drugs by scaling to the within-subject variability of the reference product in the study, and imposes a limit of 0.8 to 1.25 on the geometric mean ratio. The within-subject variability of the reference product is determined in a 3-way modified replicate-design study in which the reference product is given twice and the test product is given once. For general information on this approach, please refer to Haidar et al., Bioequivalence Approaches for Highly Variable Drugs and Drug Products, Pharm. Res. 25:237-241(2008).

Both from the wording and also from this presentation I would guess that scaling is acceptable both for C_max and AUC!

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Other candidates: Lovastatin/Niacin (Dec 2008), Alendronate Sodium (Apr 2009).

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Update Lansoprazole: Draft 05/2009, Revision 07/2009.