EBE-EFPIA Reflection Paper: An Industry Perspective on Article 117 of the EU Medical Devices Regulation and the Impact on how Medicines are Assessed
With the publication of the new Regulation on Medical Devices (MDR, Regulation (EU) 2017/745) comes an important amendment to the medicines legislation, in Article 117. As part of the marketing authorisation application (MAA) for a medicinal product regarded as an integral drug-device combination product, this article requires the Marketing Authorisation Holder to provide a Notified Body (NB) opinion for the device constituent.
Within the current regulatory landscape, guidance which covers requirements for registration of pharmaceuticals such as ICH M4Q, does not sufficiently address the Module 3 considerations to ensure registration of an integral drug-device combination product. In the absence of such key guidance, it is known that location of information related to the device component, as well as specifically what level of details is submitted, is variable across companies, which was highlighted through a recent EBE reflection paper.
The MDR becomes legally enforced on May 26, 2020 and with this, the need to incorporate a NB opinion, but it is unclear how information for that assessment will be positioned against the medicinal product MAA dossier review by the Medicines Competent Authorities (CA). Moreover, what information specifically would be the focus of the NB opinion versus that of the integral drug-device combination product by the Medicines Competent Authorities is not defined. Where a device is also a component of an already marketed medicinal product, there is opportunity to leverage prior knowledge and previous NB opinion without the need for further oversight. Furthermore, and of equal importance, there is currently no understanding of how the process to support this new requirement would work or what is the proposed timing of such assessment relative to the MAA itself, which is a critical issue for manufacturers. In turn, concerns are being raised that this could impact approval timelines and unduly delay important medicines getting to market.
Following publication of a concept paper in November 2016, the EMA Quality and Biologics Working Parties are in the process of developing a quality guidance which is hoped will address many of these gaps, in conjunction with a number of Implementing and Delegated Acts being defined to facilitate interpretation and implementation of the new legislation, but the timeframe for these being available is also not currently defined.
This paper considers these technical and procedural concerns and challenges being discussed amongst industry, with a view that recommendations made are taken into consideration as guidance and implementing acts related to integral drug-device combination products get defined. Consideration is given to the combined Advanced Therapy Medicinal Products (cATMPs) guidance on “Procedural advice on the evaluation of combined advanced therapy medicinal products and the consultation of Notified Bodies in accordance with Article 9 of Regulation (EC) No 1394/2007” which utilises a NB within the overall review and approval of cATMPs when they incorporate a medical device. With some enhancements, it is felt this procedure could be a good basis to move forward for drug-device combinations and meeting the specific requirement of Article 117. In addition, focus is given to the requirements of the NB opinion, specifically what it will cover and moreover, in relation to the CA/MAA review. Furthermore, discussion on whether Article 117 and specifically the NB opinion will include review of the manufacturers quality management system and specifically being certified to ISO 13485 is discussed.