4.1 General Description
Advances and diffusion of innovative solutions in medicine have led to discussion about interpretation and application of the past Directives related to medical devices (Directives 93/42/EEC and 2007/47/EC). In this context, a new regulatory framework which governs market access to the European Union has been planned and implemented to provide legislation aligned as much as possible to technological evolution and that could be uniform throughout the EU panorama. MDR (EU) 2017/745 Medical Devices Regulation was officially published on May 5, 2017 and entered into force on May 26, 2017. The legislation provides a three-year transition time (extended by 1 year due to the COVID-19 pandemic, until May 26, 2021) to meet the requirements of the MDR and allow manufacturers to place medical devices on the EU market following new rules. In contrast to the past Directives, regulations are directly applicable into national law, thus, reducing discrepancies around the European Union. In general, no requirements from the Directives have been removed and MDR added new ones. It is worth noting that all the medical devices have to be re-certified according to the new process, introducing a life-cycle approach to safety, supported by data.
4.2 Main Changes in Legislation Impacting the Activities of Clinicians and Scientists
MDR was created as a real new Certification with further requirements (e.g., obligation for the manufacturers of a new role, within the organization, responsible for regulatory compliance) and stricter measures (e.g., more rigorous post-market surveillance and vigilance) in line with the current global medical device market. More specifically, the introduction of new requirements aims to guarantee the safety of users thanks to greater transparency and better traceability of medical devices. Among the changes introduced by the new Regulation, some aspects are worth underlining due to their potential impact on activities performed by clinicians and scientists and will be described in the next paragraphs.
4.2.1 Classification Rules and Scope Expansion
Medical devices are classified according to a risk-based approach considering safety of users a priority and evaluating the potential risks associated with use of the device. This framework adopts criteria (e.g., invasiveness, source of energy, potential toxicity etc.), named “classification rules” (Annex VIII of MDR). These criteria lead to four main classes: I (lowest risk), IIa, IIb, III (highest risk), see Fig. 3. MDR has a wider scope and reclassifies some types of systems with respect to the previous Directives. For instance, the Regulation refers to techniques for disinfecting and sterilizing other medical devices that previously were not included. An interesting example related to innovative approaches widely adopted in medicine and in vascular ageing assessment is the higher attention placed on Medical Device Software (MDSW). Qualification has been made clearer, since “software which is intended to process, analyze, create or modify medical information” may be defined as a medical device “if the creation or modification of that information is governed by a medical intended purpose” [10]. In addition, a new classification rule (MDR rule 11, annex VIII) specifically for software has been introduced and it provides more explicit requirements than in the past. These changes will lead to a clarification for the qualification of some tools as medical devices and the update of many medical software products, already approved, to classes of higher risk and therefore to more complex certification processes. As a consequence, a more rigorous development and maintenance process for these is required. The clarification and re-classification have an impact on the activities of all involved actors starting from the design phase.
4.2.2 Explicit Obligation of a System for Risk Management
Risk has to be managed not only in the classification phase, but for the whole lifecycle of a device. MDR (Article 10, 2) requires Manufacturers to establish, document, implement and maintain a safety risk management system for the product. Risks associated with the device, including those related to human factors, must be reduced as far as possible and a process for risk management must be implemented. All residual risks must be outbalanced by the benefits related to the intended use of the device and risk mitigations must be effective throughout the life of the device. This transversal approach implies that risk-related requirements must be considered since the design phase, where inventors, clinicians and scientists might be involved. Moreover, the users’ role and their feedback are crucial and required for the whole lifecycle of the device. Finally, the value of the device introduced on the market needs to be described in terms of “clinical benefit leading to positive impact on patient-relevant clinical outcome” [2, 11]. Clearly, this is a complex process involving not only the manufacturer but the whole scientific community whose experiences and areas of expertise play a fundamental role.
4.2.3 More Rigorous Clinical Evidence About Safety and Performance
Clinical Evaluation is strictly related to the risk management mentioned above. MDR requires a more systematic approach and underlines the importance of planning and performing this activity, based on clinical data that provide evidence about safety and performance, as well as on the acceptability of the benefit-risk in adopting it. The process is based on the collection and assessment of data relating to a specific device. The analysis can include already existing data (e.g., related to similar or equivalent devices) or new data (Fig. 4). The need for new studies in humans, named clinical investigations, depends on the ability of existing data to adequately address the benefit/risk profile, claims, and side-effects to comply with the applicable Requirements [6]. The key role of a sponsor of a clinical investigation is clearly stated in MDR Article 2(49), as: “any individual, company, institution or organization which takes responsibility for the initiation, for the management and setting up of the financing of the clinical investigation” [2]. Once a system is approved for use, clinical data have to be continuously updated through a post-market activity. It is worth noting that this complex work is also based on the contributions of several stakeholders and requires the support of independent and qualified personnel [12,13,14]. Moreover, evidence derived by the adoption of an independent medical device registry could be valuable for the whole process.
4.2.4 Creation of a Framework for Traceability
The new Regulation reinforces and supports the implementation of device traceability with the introduction of the UDI system (unique device identification, Art 28), a unique numeric or alphanumeric code [15]. In addition, MDR introduces Eudamed (https://ec.europa.eu/tools/eudamed/#/screen/home, Art. 33–34). It is a platform aimed to collect key information from all EU countries in a single publicly available database. This database will allow to monitor the safety and performance of medical devices available on the EU market and to improve transparency of data related to them. Eudamed includes six main modules related to: stakeholder registration, unique device identification (UDI) and device registration, notified bodies and certificates, clinical investigations and performance studies, vigilance and market surveillance.
These tools implement a model that requires efforts by the actors and provides more information to everybody than in the past. The approach is based on more rigorous post market activities and more data available for the Society, without discrepancy around EU. It aims to reinforced traceability and transparency for the medical devices market, an improvement strongly suggested and discussed, especially for high-risk systems, by the Scientific Community [16,17,18].
