Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System

作者：Ramirez Elena; Laosa Olga; Guerra Pedro; Duque Blanca; Mosquera Beatriz; Borobia Alberto M; Lei Suhua H; Carcas Antonio J; Frias Jesus^*

来源：British Journal of Clinical Pharmacology, 2010, 70(5): 694-702.

DOI：10.1111/j.1365-2125.2010.03757.x

• bioequivalence studies
• biopharmaceutics classification system

center dot In USA and Europe the classical way to guarantee equivalence between different formulations is the bioequivalence (BE) study based on in vivo bioavailability.
center dot The Biopharmaceutic Classification System (BCS) classifies active substances into four different groups according to their aqueous solubility and intestinal permeability.
center dot Recently the European Medicines Agency (EMA) has released a new bioequivalence guideline for immediate release solid oral dosage forms that includes recommendations on BCS-based biowaivers.
WHAT THIS STUDY ADDS
center dot As far as we know this is the first time that the probability of proving BE of more than one hundred BE studies with 80 active substances categorized according to BCS was evaluated.
center dot Despite the usually employed test dissolution methodology proposed as quality control, pharmaceutical products with active substances from the four classes of BCS showed non-BE studies.
AIM
The aim of this study was to evaluate the acceptability of 124 bioequivalence (BE) studies with 80 active substances categorized according to the Biopharmaceutics Classification System (BCS) in order to establish if there were different probabilities of proving BE between the different BCS classes.
METHODS
We evaluated the differences between pharmaceutical products with active substances from different BCS classes in terms of acceptability, number of subjects in the study (n), the point estimates, and intra- and inter-subject coefficients of variation data from BE studies with generic products.
RESULTS
Out of 124 BE studies 89 (71.77%) were performed with pharmaceutical products containing active substances classified by the BCS. In all BCS classes there were non-bioequivalent pharmaceutical products: 4 out of 26 (15.38%) in class 1, 14 out of 28 (50%) in class 2, 3 out of 22 (13.63%) in class 3 and 1 out of 13 (7.69%) in class 4. When we removed those pharmaceutical products in which intra-subject variability was higher than predicted (2 in class 1 active substances, 9 in class 2 and 2 in class 3) there were still non-BE pharmaceutical products in classes 1, 2 and 3.
CONCLUSIONS
Comparisons between pharmaceutical products with active substances from the four BCS classes have not allowed us to define differential characteristics of each class in terms of n, inter and intra-subject variability for C-max or AUC. Despite the usually employed test dissolution methodology proposed as quality control, pharmaceutical products with active substances from the four classes of BCS showed non-BE studies.

• 出版日期2010-11