Establishing medical plausibility in the context of orphan medicines designation in the European Union.

Stelios Tsigkos,Kerstin Westermark,Bruno Sepodes,Laura Fregonese,Jordi Llinares,Segundo Mariz,Stiina Aarum,Naumann-Winter Frauke

doi:10.1186/s13023-014-0175-8

Abstract

In the European Union, sponsors have the responsibility to demonstrate the “intention to diagnose, prevent or treat” a serious and rare condition before the Committee of Orphan Medicinal Products (COMP), for a medicinal product to meet the criteria for Orphan Designation. This requirement is commonly referred to as “medical plausibility” and the justification of this intention is assessed on the merits of each application by the COMP, which deliberates over the scientific evaluation of the evidence submitted. The scientific assessment of the applications for orphan designation by the Committee is based on the review of non-clinical (such as in vitro and in vivo) and/or clinical data submitted by the sponsor. Several challenges regarding the evidence provided emerge when the sponsor is applying for a designation at an early stage of development. Herein we discuss specific examples from the experience of the COMP, in order to elaborate on the type and level of evidence generally considered necessary for the purpose of justification of the intention to treat an orphan condition. Importantly, it is pointed out that bridging of data from other products, irrespectively of how comparable they may be, or from settings not directly associated with the condition as applied for designation, is by and large not a successful exercise and may only be exceptionally considered. It is further exemplified that, as reflected in the updated ‘Guideline on the format and context of the applications for designation’ and the guidance document ‘Recommendation on elements required to support the medical plausibility and the assumption of significant benefit for an orphan designation’ available on the EMA website, the sponsor should provide data with the specific product as applied for in specific models of the condition or in patients affected by the same condition subject of each application.

Highlights

In order to incentivise the development of medicinal products for rare conditions that would not otherwise attract attention by the pharmaceutical industry, a European framework for “orphan medicinal products” has been put in place for more than a decade
In the EU orphan regulatory practice, this intention to diagnose, prevent or treat is referred to as “medical plausibility”, and as such cited in the respective guideline, which expects data to be presented by the sponsors to confirm the feasibility of the proposal [2,3]
Examples of successful justification of medical plausibility Justification based on preclinical data Preclinical data have been used in establishing medical plausibility within the context of an orphan medicinal product designation

Summary

Introduction

In order to incentivise the development of medicinal products for rare conditions that would not otherwise attract attention by the pharmaceutical industry, a European framework for “orphan medicinal products” has been put in place for more than a decade now. In the EU orphan regulatory practice, this intention to diagnose, prevent or treat is referred to as “medical plausibility”, and as such cited in the respective guideline, which expects data to be presented by the sponsors to confirm the feasibility of the proposal [2,3]. In this manuscript the terms “intention to treat”, as appearing in the orphan regulatory jargon and “medical plausibility” are used interchangeably. The reader is advised not to confuse this “intention to diagnose, prevent or treat”

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