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 : 1299 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. 




上一筆 Which CTD section should the reports of bioanalytical and analytical methods for
下一筆 What document should be submitted for system suitability of the dissolution assem