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balakotu ★ India, 2012-11-14 10:49 (4171 d 00:59 ago) Posting: # 9532 Views: 3,267 |
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Dear all, Please suggest the criteria for opting Replicate study design for Brazil submission. What is the BE criterion for Replicate study designs (2 treatments, 4 periods replicate) for Brazil submission. Whether for Brazil the BE criterion is similar to Europe approach or USA approach? As per Brazil guideline “Evidence Guide for relative bioavailability/bioequivalence medicines” it is given in statistical analysis section 3.2 (f) that “Other limits of 90% CI for Cmax, previously established in the protocol, may be accepted by scientific justifications”. The above criterion given is for two-way cross over study. The same is applicable for replicate studies are not. Please specify. Regards Kotu. |
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Helmut ★★★   Vienna, Austria, 2012-11-14 16:02 (4170 d 19:46 ago) @ balakotu Posting: # 9533 Views: 2,927 |
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Dear Kotu! ❝ Whether for Brazil the BE criterion is similar to Europe approach or USA approach? AFAIK neither; i.e., no scaling. ❝ What is the BE criterion for Replicate study designs (2 treatments, 4 periods replicate) for Brazil submission. ❝ As per Brazil guideline “Evidence Guide for relative bioavailability/bioequivalence medicines” it is given in statistical analysis section 3.2 (f) that “Other limits of 90% CI for Cmax, previously established in the protocol, may be accepted by scientific justifications”. ❝ The above criterion given is for two-way cross over study. No, section 3.2 deals with all types of designs. ❝ The same is applicable for replicate studies are not. See above. Resolution 898 (29 May 2003) suggests replicated designs for CVintra ≥30%. Resolutions 896 (29 May 2003) and 1170 (19 April 2006) you quoted above allow other (=wider) acceptance limits – but already fixed in the protocol. This is not reference-scaling (like for the FDA and EMA), where these limits are based on CVWR estimated in the study. I guess this method is similar to the one mentioned in the obsolte European Q&A-document from 2006 where 75–133% for Cmax were acceptable if CVWR >30% was shown in a replicate design. But: ANVISA’s website is a black hole (sink of information) and the above may be outdated. If you want to be sure send an e-mail to ![[image]](img/email.png) bioequivalencia![[image]](https://static.bebac.at/img/at.png) anvisa.gov.br.— Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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luvblooms ★★ India, 2012-11-16 06:27 (4169 d 05:21 ago) @ Helmut Posting: # 9536 Views: 2,691 |
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Dear Kotu and Helmut Recently we submitted our protocol for a Replicate study designs (2 treatments, 4 periods replicate) of one Highly variable drug product (ISCV~45%) and asked for their opinion on the widening criteria. And they royally rejected the idea of widening the Cmax quoting that they have a successful BE results with 44 volunteers in a 2 way crossover study thus we need to fulfill the same criteria  — ~A happy Soul~ |
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Helmut ★★★ Vienna, Austria, 2012-11-16 15:14 (4168 d 20:35 ago) @ luvblooms Posting: # 9542 Views: 2,442 |
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Dear LuV, this is nasty, IMHO. Even if in the 2×2 cross-over the CV was also ~45%, the study might have passed by pure chance (AR 80–125%, T/R 100% ⇒ power 55%). ~15 years ago I saw a case where the Finnish authority didn’t accept widening because they had many (!) studies in their files with (much) lower variability than the applicant’s. But to base the rejection on a single study…  — 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 |
Ing. Helmut Schütz