AUC <5% of TEST geometric mean AUC [Outliers]

posted by vezz – Erba (CO), Italy, 2019-02-13 09:35 (1984 d 04:26 ago) – Posting: # 19903
Views: 4,243

Several years ago I asked a question on a very similar issue and I think that most of the considerations made at that time applies also to the case that I would like to bring to your attention today. However, the situation is not exactly the same and in the meanwhile you may have gained some useful experience in the application of the EMA guideline on BE.

In a bioequivalence study on an orally inhaled product a case of AUC <5% of the geometric mean AUC was found for the test drug. At the time of the data review it was decided to exclude from the statistical analysis the data from this treatment period. Now the EMA is raising some concerns on this approach.

Of course, we know that the EMA guideline (section 4.1.8) allows for similar exclusions only for the reference product. However, with inhaled products it is not unusual to encounter this kind of issues, often due to a poor inhalation technique of the subject (despite the trainings provided during the study). This situation is very different compared to, say, the intake of a tablet.

I would like to ask you if you have some experiences or considerations to share on this topic.

Thank you very much for your help!

Kind regards,


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