ODs assessment in the centralized procedure: Conditional and exceptional approvals and follow up measures – Rules and experiences

Having achieved orphan designation, sponsors complete clinical investigations and submit the outcome of these investigations to the regulatory authorities to gain marketing authorisations. The (mandated) centralised review process for such applications is similar to that for non-orphan applications, relying on demonstration of adequate product quality, clinical safety and efficacy. However, due to the rarity of the condition under investigation it is likely that the data package provided with respect to clinical safety and efficacy will be more limited and may lead to the CHMP having to work with the PDCO to assess whether benefit risk has been appropriately demonstrated to the full extent possible and whether conditions should be placed on any marketing authorisation issued due to the limited available evidence. This may lead to conditional or exceptional marketing authorisation approvals where the company is either able or unable (respectively) to eventually provide a complete evidence package. Such approval status for an orphan drug would have to be clearly highlighted in corresponding labelling and would require more regular reporting of safety experience due to a less well documented risk profile for the product. In addition companies may be required to commit to further clinical investigations to the extent permitted by the prevalence of the disease. These post marketing conditions (PMCs) or follow up measures would be reported on a regular basis allowing a more frequent re-assessment of the current benefit risk profile of the product in the disease. Amgen has experience of approval of a non-orphan designated product gaining a conditional approval and of regulatory assessment of a marketing authorisation application for an orphan designated product.