Bioequivalence and Bioavailability Forum

Hi sciguy,

❝ ❝ Hhm, but how? If we dose-normalize your example we get e.g. 90.00-111.11%. If we don’t normalize, we get 112.50–138.89%.

❝

❝ I was thinking of the case where the sponsor wants to show their formulation (eg: 10 mg capsule) is bioequivalent to another formulation of different strength (eg: 8 mg tablet). Here, dose normalization would not be necessary because we actually want to show the capsule of this strength is BE to the tablet. Moreover, it would not be appropriate since different formulations = potentially diff f.

If you get a CI within 80–125% after 10 mg compare to 8 mg without dose-correction f is lower, right? It might be possible that (e.g. with an MR compared to an IR) you partly miss the absorption window of the drug. f will be lower.

Guidelines are tricky:
US CFR 21/5 320.1:

(d) Pharmaceutical alternatives means drug products that contain the identical therapeutic moiety, or its precursor, but not necessarily in the same amount or dosage form or as the same salt or ester.
(e) Bioequivalence means the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study. Where there is an intentional difference in rate (e.g., in certain extended release dosage forms), certain pharmaceutical equivalents or alternatives may be considered bioequivalent if there is no significant difference in the extent to which the active ingredient or moiety from each product becomes available at the site of drug action.