Toward A Regulatory Pathway for the Use of in Silico Trials in the CE Marking of Medical Devices.

In Silico Trials methodologies will play a growing and fundamental role in the development and de-risking of new medical devices in the future. While the regulatory pathway for Digital Patient and Personal Health Forecasting solutions is clear, it is more complex for In Silico Trials solutions, and therefore deserves a deeper analysis. In this position paper, we investigate the current state of the art towards the regulatory system for in silico trials applied to medical devices while exploring the European regulatory system toward this topic. We suggest that the European regulatory system should start a process of innovation: in principle to limit distorted quality by different internal processes within notified bodies, hence avoiding that the more innovative and competitive companies focus their attention on the needs of other large markets, like the USA, where the use of such radical innovations is already rapidly developing.

A European arena for joint innovation in healthcare: The Platform for Innovation of Procurement and Procurement of Innovation (PiPPi).

By 2000 the European Union (EU) had recognized that its innovation capacity was underperforming in comparison to similar competitors and trading partners. Although the EU has made an effort to stimulate public research and development (R&D) through policy tools like Pre-Commercial Procurement (PCP) and Public Procurement of Innovation (PPI), starting with the 2000 Lisbon strategy and continuing through the 2021 updated Guidance on Innovation Procurement, there has remained a gap in knowledge of and use of these tools, in particular within healthcare. The past decades have seen an explosion in the number and use of digital technologies across the entire spectrum of healthcare. Demand-driven R&D has lagged here, while new digital health R&D has largely been driven by the supply side in a linear fashion, which can have disappointing results. PCP and PPI could have big impacts on the development and uptake of innovative health technology. The Platform for Innovation of Procurement and Procurement of Innovation (PiPPi) project was a Horizon 2020-funded project that ran from December 2018 to May 2022 with a consortium including seven of Europe's premier research hospitals and the Catalan Agency for Health Information. To promote PCP and PPI, PiPPi established a virtual Community of Practice (CoP) that brings together all stakeholder groups to share and innovate around unmet healthcare needs. This perspective presents a brief history of PCP and PPI in Europe with a focus on digital innovation in healthcare before introducing the PiPPi project and its value proposition.

Scientific and regulatory evaluation of mechanistic in silico drug and disease models in drug development: Building model credibility.

The value of in silico methods in drug development and evaluation has been demonstrated repeatedly and convincingly. While their benefits are now unanimously recognized, international standards for their evaluation, accepted by all stakeholders involved, are still to be established. In this white paper, we propose a risk-informed evaluation framework for mechanistic model credibility evaluation. To properly frame the proposed verification and validation activities, concepts such as context of use, regulatory impact and risk-based analysis are discussed. To ensure common understanding between all stakeholders, an overview is provided of relevant in silico terminology used throughout this paper. To illustrate the feasibility of the proposed approach, we have applied it to three real case examples in the context of drug development, using a credibility matrix currently being tested as a quick-start tool by regulators. Altogether, this white paper provides a practical approach to model evaluation, applicable in both scientific and regulatory evaluation contexts.