Bioequivalence and Bioavailability Forum

Hello dears,

I am seeking advice on the best approach to address an Incurred Sample Reanalysis (ISR) trend failure in a bioanalytical study conducted over two years ago. At the time, we adhered to EMA guidelines, which did not require a detailed investigation of ISR trend failures. The ISR trend failure occurred in Period 2 for 6 out of 16 volunteers in this two-period study.

The study was completed, submitted to various regulatory authorities, and accepted; subsequently, the study samples were disposed of.

Recently, a new regulatory authority requested an investigation into this ISR trend failure in alignment with the updated M10 Bio­ana­ly­ti­cal Method Validation guidelines. They also requested sensitivity testing excluding the affected volunteers, and the study passed under these conditions.

We have initiated the investigation but would appreciate guidance on the recommended steps and actions to address this situation effectively.

Thanks in advance