myy ☆ Germany, 2014-04-17 17:40 (3660 d 05:01 ago) Posting: # 12851 Views: 4,326 |
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Dear all, 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? Would it be advisable to discuss with the regulatory authority the study requirements before initiating such a study? I would be grateful for your advice. Best regards |
Dr_Dan ★★ Germany, 2014-04-17 20:15 (3660 d 02:26 ago) @ myy Posting: # 12853 Views: 3,822 |
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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 — Kind regards and have a nice day Dr_Dan |
ElMaestro ★★★ Denmark, 2014-04-19 15:16 (3658 d 07:26 ago) @ myy Posting: # 12862 Views: 3,699 |
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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. — Pass or fail! ElMaestro |
myy ☆ Germany, 2014-04-19 15:43 (3658 d 06:58 ago) @ ElMaestro Posting: # 12863 Views: 3,678 |
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Dear Dr Dan, ❝ What sort of drug? And is this for EU or US or other? The antiparasitc drug ivermectin and it is for the EU. Kind regards myy |
ElMaestro ★★★ Denmark, 2014-04-19 17:12 (3658 d 05:29 ago) @ myy Posting: # 12864 Views: 3,698 |
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Hi myy, ❝ The antiparasitc drug ivermectin and it is for the EU. Ivermectin can be measured in plasma, so I don't think it is an obvious candidate for a PD-study. As Dr_Dan says, why not just forget about this current formulation; just stop the show now or alternatively re-formulate. If you seek scientific advice you may get green light to do PD, though. It will be terrible in every sense: Expensive, time-consuming, complicated, with weird statistics, and possibly involving infected patients with all what that entails with ethical issues and what not. You don't want to do it. Trust me. — Pass or fail! ElMaestro |