Clinical significance of Tmax [Regulatives / Guidelines]

posted by kumarnaidu – Mumbai, India, 2018-11-01 14:01 (1377 d 06:00 ago) – Posting: # 19516
Views: 2,552

Dear All,

According to the CHMP Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/Corr**) “if rapid release is claimed to be clinically relevant and of importance for onset of action or is related to adverse events, there should be no apparent difference in median Tmax and its variability between test and reference product.”
For example if the therapeutic indication of the product is for short-term symptomatic treatment of mild and moderate pain. Then, as such the rate of release is clinically relevant for this immediate release product. So for such product in BE study if the median Tmax is found to be lower for the test product (1.25 hours) than for the reference product (2.00 hours) although overall ranges were similar for Tmax but median is not comparable. So with a difference of 45 minutes in median Tmax, the absorption rates of Test product and Reference are not considered comparable. Considering T/R ratios is around 100 and the statistical comparison cannot be used as an argument because the study was not necessarily powered to detect a difference in Tmax. What would be the possible reasons for this difference and how we should justify why the difference is not clinically relevant?

Thanks in advance


Kumar Naidu

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