Bioequivalence and Bioavailability Forum

Dear Members,

I have a situation as below and need your opinion;

" We have a method for simultaneous estimation of drug and metabolite. During the course of analysis 4 subjects failed to meet acceptance criteria for metabolite but accepted for drug.According to the guidelines the data for drug should be accepted and used for PK & Stat. The batches were repeated for the metabolite after a gap of 30 days due to large sample size. The repeated batches were accepted for metabolite and data used for PK&Stat. With this repeat analysis, data for drug also was generated.According to in-house SOP the data for drug will not be used for PK analysis.


When the initial and repeat data of drug was compared, the difference observed was about +/- 30%.This was the case with 3 subjects out of more than 65 subjects

ISR passed with more than 95% acceptance criteria

Does this cause concern where the difference between initial and repeat analysis data is more than 30% and ISR is still meeting the acceptance criteria.

From our own experience, the final analysis was done with initial as well as repeat values and the BE was met with repeat values for drug as well as metabolite

The study was a partial replicate.

How would FDA look at such a situation.

Pl share your views

Regards
Chirag