Outlier in fully replicate BE study [Outliers]

posted by drgunasakaran1  – 2021-06-16 08:59 (40 d 17:20 ago) – Posting: # 22416
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Dear Mr Loky do,

» During bioanalysis of a fully replicate BE study for drug known to has a potential for back conversion (clopidogrel) ,one volunteer shows drug concentrations below LLOQ in 3 phases and only one phase (Reference product) shows very low drug concentration, no probability of not swallowing the tablets (mouth check was assured) what could be the reason of this results :confused:? Knowing that the ISR results for the study is accepted?

As per regulatory guidance, you can exclude this subject if the following criteria is fulfilled;
A subject with lack of any measurable concentrations or only very low plasma concentrations for reference medicinal product. A subject is considered to have very low plasma concentrations if its AUC is less than 5% of reference medicinal product geometric mean AUC (which should be calculated without inclusion of data from the outlying subject).
The exclusion of data due to this reason will only be accepted in exceptional cases and may question the validity of the trial.


Reference: EMA's Guideline on the Investigation of Bioequivalence

Also, be informed that Genetic Polymorphisms of Cytochrome P450 enzymes (CYP2C19, CYP3A, CYP2B6 and CYP1A2) and Esterases will affect the Pharmacokinetic profile of clopidogrel in some subjects.

Dr S Gunasakaran MBBS MD
Disclaimer: The replies/posts are my personal opinions and it does not represent my company views on the same.

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