Integral Drug-Device Combinations and Medical Device Regulation Article 117: The European Medicines Agency...

Integral drug-device combinations (iDDCs) are governed in the European Union (EU) under the medicinal products framework, but the medical device part must meet relevant requirements of the medical device framework. This implies increased complexity as actors with different responsibilities, expertise and priorities are involved. Regulation (EU) 2017/745 on medical devices (MDR) [1] came into effect on 26 May 2021. At the time of the repealed Council Directive 93/42/EEC on medical devices (MDD) [2], the European Medicines Agency (EMA) and EU National Competent Authorities (NCAs) were overseeing the evaluation of the quality, safety, efficacy, benefit/risk of the medicinal product and the relevant Essential Requirements according to the MDD of the integral medical device used in combination. Article 117 of the MDR introduced a fundamental change: notified bodies became responsible for assessing compliance of the integral medical device with the relevant General Safety and Performance Requirements (GSPRs), as set out in MDR Annex I. These GSPRs represent a more stringent set of requirements in comparison with the Essential Requirements in the MDD. One of the objectives of Article 117 and the MDR was to strengthen regulatory oversight of the device component of the iDDC and increase confidence in the regulatory system. Given the interface of the medicinal product and medical device legislations, the regulatory process for initial authorisation and lifecycle management of iDDCs is challenging to operate for pharmaceutical industry, EMA, EU NCAs and notified bodies. In particular, the implementation of Article 117 raised challenges to all stakeholders involved. In order to support implementation for pharmaceutical industry and EU medicines NCAs, EMA published dedicated guidance and engaged in various conferences and stakeholder meetings. EMA also facilitated discussion of issues with different actors and enhance mutual understanding and sharing of experience. Here, we present EMA's perspective on Article 117 implementation challenges and opportunities to tackle them.