Active metabolites: to measure or not to measure [Regulatives / Guidelines]

posted by Elena777 – Belarus, 2019-12-05 20:34 (983 d 12:01 ago) – Posting: # 20933
Views: 1,793

Dear All,

As per EMA, general recommendation is to evaluate BE on the basis of data for a parent compound. But does this mean that EMA experts never ask to measure active metabolites as well?

FDA sometimes recommends determination of an active metabolite without using its data for bioequivalence assessment (supportive data).

So, we have 3 options for a BE study in case of presence of a parent compound and its active metabolite in plasma:

1) to measure the parent compound only and to use its data for BE assessment;
2) to measure the parent compound and its metabolite and to use their data for BE assessment (separate assessment: 90% CI for the parent and 90% CI for the metabolite);
3) to measure the parent compound and its metabolite; to use the data obtained for the parent compound in BE assessment and to use the data for the metabolite as supportive information only without calculating 90% CI for the metabolite.

What to take into account while thinking of what to prefer? And is this always the correct and sufficient decision to use option 1 taking into account that EMA recommendations overweigh FDA recommendations in our environment?

We have had a poor experience recently: a Belarusian expert asked why the active metabolite had not been measured together with the parent (he/she would like us to use option 3). We provided some justification and now are waiting for the response from the expert.

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