Bioequivalence and Bioavailability Forum

Dear Colleagues,

For bioequivalence/bioanalytical LC-MS/MS assays we used to calculate accuracy and precision for QC samples by carrying out three samples or five samples at three concentration levels and back calculate concentrations by taking area ratios and applying regression equation. Recently, a regulatory reviewer is insisting that we calculate precision from area ratios disregarding regression equation. We examined several validated assays and found that using area ratios only resulted in huge CV% reaching up to 45% in same assays and within limits for some others.

We need your advice on how to respond to this impasse with the regulators with references.

Thanks,
Mohamed