Bioequivalence and Bioavailability Forum

Dear Deepak,

❝ I spiked metabolite for new validated method as study samples contain analyte and metabolite. HQC level of metabolite is spiked in parent analyte during method validation.

It is good to do it at least once, analysing QCs spiked only with the parent + QCs containing parent and metabolite, against calibration samples containing only the parent. This way you can demonstrate the selectivity of your method and the lack of back-conversion during the analysis. But I would not necessarily expect the whole validation to be performed with samples spiked with the metabolite if you don't measure it with the method being validated.

❝ Sponsor want to achieve targeted timelines of submission.

Yeah... Unfortunately The Man In The Armani Suit is always in a hurry...

❝ Only major difference and point of concern is that:

❝ Old method: parent analyte is only present in stability QC samples.

❝ New method: parent analyte and metabolite is also spiked in stability QC samples.

❝

❝ Whether LTS data of old method is acceptable for parent analyte as per usfda?

You did not answer my question on the type of metabolite and risk of back-conversion... If you have long-term stability data of your metabolite showing that there is no back-conversion during storage, I would think you can provide reasonable justification. I would also look at the results of the other stability experiments, particularly freeze/thaw (passing easily, or borderline ?). If in doubt, start a controlled correspondence with the FDA. But with the shutdown, running the stability might be faster