Use of biomarkers in the context of orphan medicines designation in the European Union.

The use of biomarkers within the procedures of the Committee of Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) is discussed herein. The applications for Orphan Medicinal Product designation in the EU are evaluated at two stages. At the time of orphan designation application, the file undergoes an assessment to establish whether the proposed condition is a distinct and serious condition affecting not more than 5 in 10,000 people in the EU, and whether the product is plausible as a therapy for that condition. In cases where therapies already exist, the significant benefit of the candidate product over existing therapies is also evaluated. The orphan criteria are reassessed at the time of marketing authorisation, so that marketing exclusivity for the product in the orphan medical condition can be granted. Within this context, biomarkers have been used in submissions in order to define an orphan condition and to justify that the criteria for orphan designation are met. The current work discusses specific examples from the experience of the COMP, where biomarkers have played a decisive role. Importantly, it identifies the proposal of sub-sets of non-rare conditions based on biomarkers as a challenging issue in the evaluation of applications. In particular two specific requirements for the candidate orphan medicines in relation to the biomarker-based subsets are highlighted: the "plausible link to the condition" and the "exclusion of effects outside the subset".