Bioequivalence and Bioavailability Forum

Dear myy
In applications for generic medicinal products according to Directive 2001/83/EC, Article 10(1), the concept of bioequivalence is fundamental. Two medicinal products containing the same active substance are considered bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and their bioavailabilities (rate and extent) after administration in the same molar dose lie within acceptable predefined limits. These limits are set to ensure comparable in vivo performance, i.e. similarity in terms of safety and efficacy. I am not sure if in your case a clinical endpoint study will allow bridging of preclinical tests and of clinical trials associated with the reference medicinal product since your formulation has already failed to show bioequivalence in a single-dose, two sequence and two-period crossover clinical trial. I suggest to discuss with the regulatory authority not only the study requirements before initiating a clinical endpoint study but also the submission strategy. Before doing so you should ask yourself if the substance really is a problematic compound or if you just face a formulation problem. In case competitors got marketing authorisations by means of a passing bioequivalence study you should cancel the project.
Kind regards
Dr_Dan

Hi myy,

❝ if a substance seems to be a problematic compound that has failed to show bioequivalence in a single-dose, two sequence and two-period crossover clinical trial is there a possibility of demonstrating bioequivalence using a clinical endpoint study? Does the clinical endpoint study have to meet the statistical BE criteria?

What sort of drug? And is this for EU or US or other?

❝ Would it be advisable to discuss with the regulatory authority the study requirements before initiating such a study?

Yes.