Bioequivalence and Bioavailability Forum

❝ Dear Ohlbe

Thanks for your reply.

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❝ ❝ I have developed and validated new method (changes primarily include [...] parent analyte spiked in plasma in presence of metabolite for all experiments) and performed study sample analysis with new method.

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❝ I'm not sure I understand. Did you measure the metabolite too ? If yes and as rightly pointed out by VKB2207, you need long-term stability data for the metabolite anyway, so you old data will not save you. If not, why did you add the metabolite for all experiments ? Can you give us more details on the structure of the metabolite compared to the parent compound (primary or secondary metabolite, risk of back-conversion etc.), and the levels of concentration of the metabolite compared with the parent ?

Yes. Metabolite was also measured with different method. I have LTS data for metabolite (in presence of analyte) for required duration. 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.

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❝ ❝ However I am unable to finish LTS experiment for required duration with new method.

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❝ Is this just because the sponsor is in a hurry and wants the report last week, or are there other reasons ?

Sponsor want to achieve targeted timelines of submission.

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❝ ❝ Can I use long term stability data of old method as supportive data for my usfda study submission?

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❝ Long-term stability in matrix is independent from the bioanalytical method used: if the analyte is stable for 3 months with method A it will also be stable for 3 months with method B. The FDA and EMA requirement to test for the stability of all analytes spiked together in case several drugs are given to a subject, even if stability data are available for each analyte separately (e.g. drug/drug interaction studies), is highly disputed by industry and regularly discussed at bioanalytical conferences. I didn't hear of an extension of this FDA/EMA requirement to non-measured metabolites.

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I have measured analyte and metabolite also with two different methods.

❝ However the storage conditions are important (not just the temperature, also the type of tubes used due to possible adsorption), and you should check they were the same in the old and new method.

Storage conditions and types of tubes used are same in both methods.
Only major difference and point of concern is that:
Old method: parent analyte is only present in stability QC samplpes.
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?

Awaiting your response.

Regards
Deepak Pangavahne