Bioequivalence and Bioavailability Forum

Hi everyone,

our general approach for integration of peaks in chromatograms is one generic method per batch, no smoothing and "manual" integrations.

However (as every analyst except regulators knows ), from time to time it is not so easy to integrate all chromatograms within the batch consistently with one generic method.

This time I will not focus on "manually" (though scientificaly sound) integrated chromatograms that the regulatory agencies are so afraid of and were already thoroughly discussed elsewhere, but rather on the "type" of integration method- "raw" data or/and smoothing.

Despite the fact that some agencies prefer the same integration method to be used for validation and study , our approach remains one method per batch.
If we are lucky there is indeed the same method for validation and study, but in reality, we have to adjust certain parameters such as noise level, RT, peak width etc., but never apply smoothing (again historic regulatory tabu).

If we took a rather conservative/regulated approch, which tests should/could be performed to justify that smoothing (how much?) could be applied?

I was thinking of reintegrating 3xA/P (data used for between run A/P and establishment of regression model) and then comparing the results (raw vs. smoothed data). Since I am far from a statistician expert, how to evaluate the comparison (t-test....)? IMHO, only the "classical bioanalytical" %nominal and %CV wouldn't be enough.

Anyway, would such a procedure be sufficient for regulatory agencies to allow smoothing or no-smoothing within the same validation or study.
Does anyone have any real experience on this topic?

Regards
Marko