Bioequivalence and Bioavailability Forum

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 CV_intra ≥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 CV_WR 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 C_max were acceptable if CV_WR >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But: ANVISA’s website is a black hole (sink of information) and the above may be outdated.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 bioequivalenciaanvisa.gov.br.