balakotu
★    

India,
2012-11-14 10:49
(4152 d 05:12 ago)

Posting: # 9532
Views: 3,227
 

 Replicate study design for Brazil submission [Regulatives / Guidelines]

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.
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2012-11-14 16:02
(4151 d 23:59 ago)

@ balakotu
Posting: # 9533
Views: 2,894
 

 ANVISA – likely no scaling

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But: ANVISA’s website is a black hole (sink of information) and the above may be outdated.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] bioequivalencia[image]anvisa.gov.br.

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
luvblooms
★★  

India,
2012-11-16 06:27
(4150 d 09:34 ago)

@ Helmut
Posting: # 9536
Views: 2,657
 

 ANVISA – likely no scaling

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 :blahblah:

~A happy Soul~
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2012-11-16 15:14
(4150 d 00:48 ago)

@ luvblooms
Posting: # 9542
Views: 2,410
 

 ANVISA: strange

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… :no:

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,638 registered users;
69 visitors (0 registered, 69 guests [including 8 identified bots]).
Forum time: 16:02 CET (Europe/Vienna)

Nothing shows a lack of mathematical education more
than an overly precise calculation.    Carl Friedrich Gauß

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5