Individual bioequivalence--has its time come?
A forthcoming draft Guidance of the Food and Drug Administration is expected to replace the current framework for the assessment of bioequivalence, based on the comparison of average kinetic responses, with a very different approach, the evaluation of individual bioequivalence. It emphasizes the estimation of intraindividual variances of the contrasted drug products as well as of the subject-formulation interaction, and requires the conduct of 4- (or 3-) period crossover bioequivalence trials. In order to facilitate the discussion of the draft Guidance and of the new approach, the underlying rationale, principles and procedures are described. Following this, various open questions are raised. It is suggested that their resolution should be carefully and widely discussed, and that more research and experience is needed before the possible implementation of the new approach.
Endrenyi
L
L
University of Toronto, Department of Pharmacology, and Department of Preventive Medicine and Biostatistics, Toronto Ont. M5S 1A8, Canada. l.endrenyi@utoronto.ca
Midha
K K
KK
D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration
D004364:Pharmaceutical Preparations