Different Truncation Methods of AUC between Japan and the EU for Bioequivalence Assessment: Influence on the Regulatory Judgment
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- OISHI Masayo
- Department of Drug Development Science & Clinical Evaluation, Keio University Faculty of Pharmacy
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- CHIBA Koji
- Department of Drug Development Science & Clinical Evaluation, Keio University Faculty of Pharmacy
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- FUKUSHIMA Takashi
- Department of Drug Development Science & Clinical Evaluation, Keio University Faculty of Pharmacy
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- TOMONO Yoshiro
- Department of Drug Development Science & Clinical Evaluation, Keio University Faculty of Pharmacy
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- SUWA Toshio
- Department of Drug Development Science & Clinical Evaluation, Keio University Faculty of Pharmacy
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Abstract
In regulatory guidelines for bioequivalence (BE) assessment, the definitions of AUC for primary assessment are different in ICH countries, i.e., AUC from zero to the last sampling point (AUCall) in Japan, AUC from zero to infinity (AUCinf) or AUC from zero to the last measurable point (AUClast) in the US, and AUClast in the EU. To assure sufficient accuracy of truncated AUC for BE assessment, the ratio of truncated AUC (AUCall or AUClast) to AUCinf should be more than 80% both in Japanese and EU guidelines. We investigated how the difference in the definition of truncated AUC affects BE assessment of sustained release (SR) formulation. Our simulation result demonstrated that AUCall/AUCinf could be ≥80% despite AUClast/AUCinf being <80% and AUCall failed to detect formulation difference. In Japanese package inserts of generic drugs in SR formulation, there were products for which AUCall/AUCinf was ≥80% though AUClast/AUCinf was <80%. In conclusion, it was confirmed that the difference in definition of truncated AUC affected the judgment of validity of truncated AUC for BE assessment, and AUCall could fail to detect the substantially different in vivo dissolution profile of generic drugs with SR formulation from the original drug.<br>
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 27 (6), 658-662, 2012
The Japanese Society for the Study of Xenobiotics
