New FDA bioavailability guidance [BE/BA News]

posted by zizou – Plzeň, Czech Republic, 2022-04-16 18:22 (40 d 23:15 ago) – Posting: # 22934
Views: 552

Hello.

What suprised me is a change of rounding of CI in Appendix A (last point).

Draft:

1024 Rounding off of confidence interval values
1025
1026 We recommend that applicants not round off CI values; therefore, to pass a CI limit of 80 to 125
1027 percent, the value should be at least 80.00 percent and not more than 125.00 percent.


Final:

G. Confidence Interval Values for Unscaled Average Bioequivalence Analyses

Sponsors should round off CI values to two decimal places. For unscaled average bioequivalence analyses, to pass a confidence interval limit of 80 to 125 percent, the rounded confidence interval value should be at least 80.00 percent and not more than 125.00. We thus recommend that when applicants evaluate the confidence interval to assess bioequivalence using an unscaled average bioequivalence analysis during the development program, applicants round confidence interval values to two digits after the decimal point.


This change is equivalent to the change of acceptance interval from [80,125] to [79.995,125.005). So we can correct acceptance limits in sample size calculations (just to be exact) and also edit the procedure (coded in statistical software) with comparison of exact values of CI with acceptance limits (round CI before comparison or equivalently change the acceptance limits).
So it will be the same as according to EMA guideline now.

I was hoping for the change of EMA guideline to not round off CI values. Now, I would write the acceptance interval [79.995,125.005) in the study protocols as these values are exact and no questions about TIE > 5 % can arise! ;D

Best regards,
zizou

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