For the bioequivalence study of highly variable drug, in what circumstances that the 90% CI of the Cmax can be widened to 0.75~1.33?

刊登日期:2019-10-25  |  點閱次數 : 1635 次 

According to Article 18 of the Regulation of Bioavailability and Bioequivalence Studies, for drugs with high intra-subject variability and not classified as narrow therapeutic index (NTI), the acceptance criteria for the 90% confidence interval of Cmax can be widened to 0.75 to 1.33; in such case, the implication of international guidelines and clear statement in the study protocol will be required. If the high intra-subject variability (larger than 30% or SWR≧0.294) of the Cmax for reference product is confirmed under a reference replicated cross-over study, the acceptance criteria could be widened to a range of 0.75 to 1.33. If the observed intra-subject variability of Cmax is not more than 30% (or SWR<0.294), 90% CI should be based on a range of 0.80-1.25. The applicant should justify that the calculated intra-subject variability is a reliable estimate and that it is not the result of outliers. The request for widened interval must be prospectively specified in the protocol. 




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