Brought about at least in part by the PIP silicone implant scandal of the late 1990s and early 2000s, the overhaul of the European medical device regulations which resulted in the introduction of the MDR (Medical Device Regulation) has been underway for many years. As an engineer working in medical device development I find it an interesting case study in regulatory change and the uncertainty that comes with it.
The proposal for new regulation was adopted in 2012 and in subsequent years draft documents and guidance have become available. These provided details of the direction in which the regulation was heading, and it was evident that there would be a significant increased burden falling on device manufacturers, for example:
• The extension of the MDD requirement for a Clinical Evaluation Report (CER) such that it must now include the results of clinical investigations, refer to conclusions on the safety and performance of the device and a risk benefit analysis. Claims of equivalence to other devices so as to leverage existing clinical studies will be more rigorously interpreted.
• The need for the CER to be maintained through the life of the device, with regular reviews and updates based on post market clinical follow-up and post market surveillance. The MDR promotes this lifecycle approach, as opposed to a single pre-approval process.
• The requirement for a person responsible for regulatory compliance, with specific qualifications and/or experience, who needs to be “within the organisation”.
• The addition of device and manufacturer identifiers to all device labelling, including for software.
For manufacturers of inhalation devices, the introduction of a new classification rule also has significant implications, as “Invasive devices which are intended to administer medicinal products by inhalation” will now be classified as Class IIa or, dependent on risk profile, Class IIb devices. Non-active inhalation devices under MDD were designated as Class I and could hence be self-certified, but now review by Notified Body will be required.
The regulation came into force in May 2017, with a three year transition period until May 2020 during which MDD and AIMDD will still operate. At the time of writing we are well over halfway through this period, yet uncertainty remains in some key areas. The MDR is a hot topic, at industry conferences and forums run by organisations such as IPAC-RS and TOPRA. These cross-company discussions seek to establish some level of clarity – or at least industry interpretation and consensus – on how the regulations will be implemented in practice. But they frequently result in questions being raised to which the industry itself cannot provide the answers. In early 2019 these questions included:
• Article 117 of the MDR, which relates to the amendment to Annex 1 of the Medicinal Product Directive, dictates that the device constituent part of a Medicinal Product, where it is integrated non-reusable and intended for use exclusively in a given combination, must meet MDR Requirements for General Safety and Performance. This goes further than the MDD which requires that Essential Performance Requirements are fulfilled, and in some eyes effectively approaches CE Marking. But how will Article 117 be interpreted in practice, and how consistently?
• With significant increased burden also falling on Notified Bodies, including granting of an opinion on Annex 1 and generation of clinical evaluation assessment reports (CEARs), what will the availability and capacity be of those with the appropriate expertise? What might the impact be on timescales for getting a product to market?
• At what point is Notified Body opinion required, for example before submission or in parallel with it?
• What will a rejection from a Notified Body look like? For example will it be detailed and constructive or brief and less helpful? Will it be consistent across Notified Bodies? Will it be made public? As time moves on the industry further debates these and other issues and additional guidance is forthcoming. In October 2018 five guidance documents on device identifiers alone were issued by the European Commission. In the meantime manufacturers are constantly assessing the implications for new product submissions and also, potentially, for existing approved products. It has been made clear that there can be no ‘grandfathering’, such that after the grace period all CE Marked devices must conform to the MDR. 
And although this does not include currently authorised medicinal products with an integral medical device, where the requirements of Article 117 will not be applied retrospectively, this is only the case if there is no substantial change to the design or intended purpose of the device component. But is it clear what will be considered to be a substantial change? Decisions on which strategies to adopt for new device approvals, and for recertification or discontinuation of existing legacy devices, are having to be taken in the current climate of uncertainty. Companies would no doubt prefer to delay until full clarity is achieved, but this could still be some years away.
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