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In vitro diagnostic medical devices (IVD): from the Directive to the Regulation 2017/746

The transition from the old Directive on in vitro diagnostic medical devices 98/79/EC (IVDD) to the new Regulation 2017/746 (IVDR), which will apply from May 26th 2022, will be more of a landmark than the transition from the Directive on medical devices 93/42/EEC (MDD) to its new Regulation 2017/745 (MDR).

Whereas for medical devices, the new MDR represents a systematizing upgrade of many arrangements, positions, procedures and decisions already variously existent in the regulatory landscape (plus new prescriptions that conversely can be also considered as technical extensions rather than new orientations), if not predictable remedies to experiences gained through the years (from scandals to borderline practices), many changes introduced by IVDR with respect to the old IVDD are real novelties (of directions other than of technicalities).

The most striking are the introduction of risks classes (increasing from A to D) and the systematization of all activities related to the demonstration of clinical performances, first of all the (interventional) clinical study that will establish itself as the counterpart of clinical trials but in the framework of IVD. This one will also directly influence the activities of third parties, as Ethical Committees in charge of approving study applications at the clinical level and as Competent Authorities of Member States that authorize the study.

The new centralized system of registrations and, in general, of management and transfer of information on IVD borrows the same structure of medical devices. Eudamed already existed before the two new regulations, although it never reached full operation. The new identification system based on UDI also comes from previous Union guidelines and it goes hand in hand with the FDA system, both aligned to agreements among regulators gathered in the IMDRF. The more extensive language on the obligations falling on the whole supply chain, from manufacturers to importers and distributors (economic operators), absent up to date, comes from the guideline given by Decision n.768/2008/EC and it mainly represents a change of operational habits for all the involved parties, strengthened by the awareness that national legislations of Member States have already ruled largely in judicial courts on the responsibilities of the various parties, independently from and beyond the lex specialis in the sector. Provision of services and distance sales (internet) are regulated essentially to keep pace with the new forms of social connections (and it will be interesting to observe the efficacy of their practical enforcements and control measures throughout the Union, just by considering that, for years, many economic operators have been unarmed and unprotected victims of the internet jungle due to national and international inability to provide something north of a complete deregulation level). The new role of the person responsible for regulatory compliance, inspired by the pharmaceutical world, will be the hybrid, partly technical and a bit administrative, whose legal responsibilities will be kept at the Member State national level, and thus being still an unknown waiting for future developments.

As anticipated, the introduction of the risk class concept of an IVD is a novelty that will change the way the products are managed. The old IVDD provided for only two lists with precise indication of 21 targeted situations (from the ABO system to the Creutzfeldt-Jakob disease, from the anti-Duffy to the blood sugar). Vice versa, with the risk class increasing from A to D, it became possible to introduce rules of classification that generalized the approach to IVD frameworking, thus moving from a preventive identification of given situations to an open system. A clear consequence will be the rise of CE certifications needed for the placing on the market, given that Notified Body (NB) intervention is established already for class B products. MedTech estimates that certifications will move from present 10% to future 85% of all marketed IVDs, quite not a negligible jump. In fact, MedTech already took its stance on the necessity of reviewing the approach to the management of this ongoing transition phase, both for medical devices and IVDs, given that the quantity of NBs available to certify does not seem to be sufficient to cover the whole sector, thus fomenting an outlook of uncertainties for companies and (hypothetically) for the system stability.

By considering the changes introduced in the processes of conformity assessments, quite more complex both for manufacturers and NBs, it is predictable that the products being equal the time necessary to get to certification will lengthen with respect to old IVDD. A properly defined transition phase should guarantee the possibility to transit, but if the are no NBs available in the transition phase, it goes without saying that the phase should be considered dead or ineffective. It is not sufficient that NBs will start their activity at the date of application of IVDR, but it would be necessary for them to operate already before that date and in appropriate amount. This aspect, in common with medical devices as defined by Reg. 2017/745, was already known by the legislator, it is sufficient to recall preamble (95) of IVDR, while hoping not to make use of it but being aware of the likeliness of its prophetic value.

The second identifying aspect of the new IVDR is the taking charge of the area related to studies with IVDs, as counterpart of clinical investigations with medical devices. Until now this sphere has not been regulated, given that the old IVDD at Art.9(4) establishes loose minimum requirements and it remits to national legislations. Vice versa, IVDR provides for a more complete and comprehensive legislative framework, with the aim at regulating the entire management of IVD studies at the Union level, ultimately making the sector uniform. It is understood the acknowledgement of the scientific and technical developments of IVDs with respect to the times of the old IVDD implementation. Today, in vitro diagnostics presents itself as a sector of highly prolific possibilities and solutions, only hypothetical in the past, thus it has been the legislator goal to foresee its developments and regulate its processes. At the same time though, more evolution implies more relevance, that is more responsibilities deriving from constantly rising resort to IVDs for diagnostic and therapeutic management of patients. In this perspective it gets easier to understand the origins and purposes of the new provisions, without doubt impacting on manufacturers operations and resources: from the post-marketing performance follow-up (PMPF) to the post-marketing surveillance system (PMS), from post-marketing surveillance update reports PSUR) to the summary of safety and performance, from the new procedures in the field of vigilance management to the trend reports. Everything revolves around the transfer of evidences from the scientific to the utilitarian level, while passing through the guarantee of an acceptable level of safety for patients, overlooked by the MDCG (already established for medical devices) and by Experts groups, as well as by the EU reference laboratories.