Bioequivalence and Bioavailability Forum

Great story, Helmut,

thanks for posting.
What surprises me somewhat is this:

• The mean AUC for the 24 healthy adult volunteers after administration of Budeprion XL 300 mg was 86% (90% CI, 76.7-95.8%) of the value determined after administration of Wellbutrin XL 300 mg.
  
• The corresponding Cmax value for Budeprion XL 300 mg was 75% of the value for Wellbutrin XL 300 mg (90% CI, 65.2-86.8%).

A BE study generally has three possible outcomes: Bioeequivalent, bioinequivalent (CI entirely outside acceptance range) or inconclusive (overlap with the acceptance range, meaning not proven bioinequivalent and not proven bioequivalent). The latter applies here, yet the action taken by the regulators suggests they consider the products inequivalent. If I were the FDA and had the funds I would certainly run a new study with more subjects in order to reach a firm conclusion.

Of course, if the stats obtained with N=24 are correct then the chance of showing bioinequivalence is higher than the chance of showing bioequivalence, that's clear (and yes, how to calculate the sample size when the previous T/R was lower than 80% is an issue, but let's not go there). Bioinequivalence hasn't been shown until the CI is entirely out of the acceptance range, and as I read the announcement from FDA they also do not use wording suggesting that the products are truly inequivalent. In stead they just correctly suggest that BE has not been shown.

Another case of 'aggregate weight of evidence', I imagine.