The new Medical Device Regulation (MDR) have been approved on May 2017 and the date for its implementation was May 2020, but recently its implementation was postponed due to the Corona pandemic and currently the target date is May 2021.

In this Newsletter, I will briefly highlight the changes in the new regulation related to clinical data collection.Beyond the many changes in aspects such as: new classifications, risk levels, Notified Bodies, certification processes and more, clinical evaluation requirements have been updated as well. The new regulation requires now a constant "live" connection between the risk management and the Clinical Evaluation and requires adjustment of the risk management processes and interphase with the clinical evaluation.                               

The sponsor is essentially required to assess each risk through clinical investigations, clinical evaluations, and of course through post-market clinical follow-up. Overall, referring to risk management, the MDR is in alignment with EN ISO 14971:2019 and EN ISO 13485:2016. While developing or amending the clinical plan, it should be taken into account that any change derived from the new regulation may also have implications on the clinical program. I.e. the question of medical device classification can have such implications and it is therefore advisable to characterize these implications before establishing the clinical program.

The transition from MDD (Medical Device Directive) to MDR has resulted in significant additional information in aspects of clinical data collection which is manifested in 20 new articles (articles 62-82). For Europe these are a fundamental changes and alignment with norms that are accepted worldwide in the medical device arena. The additional articles specify in fact requirements that have been relatively ambiguous so far, among other things, they specify requirements regarding:

●the responsibility of the sponsor;

●ethical considerations;

●subject consent process;

●reference to vulnerable populations;

●safety information reports;

●insurance etc.

In addition to these articles Annex XV, which extend the MDD Annex X, explains what information is required to appear in various core documents such as:

●Clinical investigation report,

●Investigator`s Brochure,

●Clinical Investigation plan and others.

In terms of definitions, the MDR defined “Clinical Evidence”, extend the equivalence requirements to be more stringent and increased oversight of PMS (Post Marketing Surveillance) data. Despite the considerable extensions, more detailed standards and requirements will be found in the ISO 14155 and of course in ICH GCP.

Article 61 provides a concrete requirement for the need to conduct clinical trials with reference to implants or Class III For the other classifications, the requirement for conducting clinical trials is derived from the level of clinical information collected by the sponsor throughout the life cycle of the product. It is the responsibility of the sponsor to characterize the Clinical Evidence required for the product according to its characteristics and intended use. Given that the clinical information is limited, additional data, based on clinical investigation conducted in accordance with the GCP Guidelines, ISO 14155: 2011 and the Declaration of Helsinki would be required to complete gaps.

Article 62 indicates potential purposes for the clinical trial, these operations should be performed under the product design, the "normal" conditions of its intended use, including manufacturing and packaging. The clinical operations may be carried out to characterize the performance, benefits of its use as well as its safety implications. The structure of the trial and its design will be derived from the concrete need. Those operations may be:

relatively small in scope and their purpose will be to continue learning and improving aspects of product performance (Pilot studies) or, alternatively,

more extensive operations designed to present device performance under the conditions and constraints required to its function in the intended environment (Pivotal Study). Pivotal studies will most often be performed when the product is mature and expected to function as required and present its intended performance in accordance with the Claims.

The responsibility for maintaining clinical knowledge about the product on its variety of models and versions is the sole responsibility of the sponsor. When existing clinical knowledge changes or loses its validity as a result of changes in the product, adaptation of the clinical data collection plan should be considered. That process should use existing knowledge to establish updated conclusions and characterize the gap, and clinical investigation may be executed in order to complete the gap. Usually, a solution will be found that combines these two approaches.

In conclusion, for any product intended to be marketed in Europe, a continuous clinical information collection process is required throughout the product life cycle. The aforementioned sources of information include: literature and scientific publications, clinical operations, and information gathering from marketed products. The nature of the information collected and its purpose will be defined and adjusted to the product requirements and to the risk’s assessments. This process importance is further elaborated under the new regulation and plays a critical role in the dynamic assessment of the benefits and risks of using the medical device.

In a nutshell, changes in clinical requirements under the MDR:

This Newsletter Prepared by:

Matti Hoggeg, M.Sc,

Clinical Section Manager

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