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Mahesh M
Regular

India,
2014-09-26 11:53

Posting: # 13591
Views: 2,068
 

 Multiple dose study for MR product in EU [Regulatives / Guidelines]

Dear All,

When multiple dose study is required To demonstration of Bioequivalence between two MR dosage form for EU.
The European guidance line no. 593 to 595 states as follows:

"A multiple dose study is needed unless a single dose study has been performed with the highest strength which has demonstrated that the mean AUC(0-τ) after the first dose covers more than 90% of mean AUC(0-∞) for both test and reference, and consequently a low extent of accumulation is expected".

Please elaborate or simplify the same for better understanding.

Regards
Samaya B
Junior

India,
2014-09-27 11:06

@ Mahesh M
Posting: # 13599
Views: 1,620
 

 Multiple dose study for MR product in EU

» "A multiple dose study is needed unless a single dose study has been performed with the highest strength which has demonstrated that the mean AUC(0-τ) after the first dose covers more than 90% of mean AUC(0-∞) for both test and reference, and consequently a low extent of accumulation is expected".
»
» Please elaborate or simplify the same for better understanding.

Dear Mahesh,

You can consider "first dose" as a "single dose" study.

For MR products in EMEA, first perform pivotal BE study under fasting state and evalaute the results. If AUC0-t>0.9*AUCinf, you need not to go ahead for steady state BE study. BE under steady state is required when drug accumulates in body. If AUC0-t> 0.9*AUCinf is achieved after signle dose administration, normally, there would not be accumulation.

You can refer following posts as well: #12612, #7062, #8296

Hope this info would be helpful.

Regards,
Samaya.


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut]
jalgorta
Junior

Spain,
2017-03-14 14:18
(edited by Ohlbe on 2017-03-14 17:37)

@ Samaya B
Posting: # 17156
Views: 439
 

 Multiple dose study for MR product in EU

» For MR products in EMEA, first perform pivotal BE study under fasting state and evaluate the results. If AUC0-t>0.9*AUCinf, you need not to go ahead for steady state BE study. BE under steady state is required when drug accumulates in body. If AUC0-t> 0.9*AUCinf is achieved after signle dose administration, normally, there would not be accumulation.

Hi Samaya, you mention that "first perform pivotal BE under FASTING state"... My question is if you can confirm and reference that the calculation must be under fasting. Since in the case of modified release two conditions are necessary, should be FAST and/or FED???
Kind regards


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]
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