Bioäquivalenzstudien mit hochvariablen Arzneistoffen nach der neuen Fassung der europäischen Bioäquivalenz-Leitlinie
FOCUS Clinical Drug Development GmbH, Neuss
Korrespondenz: Dr. Günther Pabst (neue Anschrift), PKPDPG Beratung UG (haftungsbeschränkt) & Co. KG, Derikumer Weg 26, 41468 Neuss (Germany), e-mail: email@example.com
The new version of the bioequivalence guidance offers for highly variable drug substances a new approach as an alternative to the standard 2-period cross-over design. Some vague phrases in the old guidance (“in certain cases . . . may be”) were converted into fixed rules. The confidence intervals now are compared to acceptance ranges which depend directly on the intra-individual variability of the reference preparation. This requires that the bioequivalence study is performed according to a repetitive design, but this design nevertheless requires fewer concentration-time profiles than a comparable 2-period cross-over design. The widening of the acceptance limits stops at 50 % intra-individual variability, but the new alternative approach also is of advantage for drug substances of even higher variability.
Key words Bioequivalence • highly variable drugs • repetitive design • sample size
pharmind 2011, Nr. 6, Seite 1146