ashokraj ☆ India, 2015-07-22 16:26 (3172 d 19:26 ago) Posting: # 15124 Views: 4,963 |
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Hi all Can any one through some light on why EMA do not allow widening of CI limits for AUC of HVDs? Whereas RSABE is applicable for AUC as well by USFDA. rgds/Ashokraj |
d_labes ★★★ Berlin, Germany, 2015-07-22 18:03 (3172 d 17:49 ago) @ ashokraj Posting: # 15125 Views: 4,188 |
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Dear Ashokraj! "The Lord moves in mysterious ways." Regulators are a strange bunch of people. IMHO there are no scientific reasons behind this decision. Helmut once called it "pure politics". And politics must not be reasonable. Search the Forum. We had already occasionally exactly that theme. — Regards, Detlew |
Helmut ★★★ Vienna, Austria, 2015-07-22 18:26 (3172 d 17:26 ago) @ ashokraj Posting: # 15128 Views: 4,265 |
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Hi Ashokraj, ❝ Can any one through some light on why EMA do not allow widening of CI limits for AUC of HVDs? Whereas RSABE is applicable for AUC as well by USFDA. There is no scientific justification for it at all. The background is a mishmash of history and politics. In the dark ages of BE a few products were approved in Europe with a widened (pre-specified) acceptance range of up to 70–143% (i.e., a 30% difference was considered not clinically relevant) for AUC. These were rare exceptions. However, widening for Cmax was pretty common (without requiring a clinical justification). The 2002 NfG stated for AUC “In rare cases a wider acceptance range may be acceptable if it is based on sound clinical justification“. In 2006 EMA backpedaled and stated that widening is acceptable only for Cmax and limited it to 75–133% (if high variability was demonstrated in a replicate design). Given the background of many products on the market approved for an AR of 70–143% for Cmax, EMA decided to cap the scaling at a CVwR of 50% in their 2010 GL. Do you see the similarity in the numbers?
Timeline and summary for AUC:
— Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |