A team of researchers of the In Silico World project, led by Prof. Francesco Pappalardo (University of Catania), investigated 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.
The results of this research have been published in the article “Toward a regulatory pathway for the use of in silico trials in the CE marking of medical devices” where the authors suggest that the European regulatory system should establish a clear pathway for the use of in silico methodologies in the development, derisking, and regulatory assessment of new medical devices. Digital Twins, patient-specific computer models can be used to virtually test the effects of a new medical device, supporting the evaluation of its safety and efficacy. These are key information for the obtainment of the CE Mark, without which no new medical device can be sold in the European Union.
With the publication of the recent FDA guidelines and of the ASME VV-40 technical standard such a pathway already exists for the USA market, but companies that plan to sell in Europe a still operating in a confused scenario, where different notified bodies may have different opinions on the use of in silico methodologies, and on how to demonstrate their credibility.
Patient-specific models can be used to support the medical decision about a specific patient. In this case, the technology is considered itself a medical device, which can be CE marked following a pathway known as software as medical device. But when these technologies are used to evaluate the safety and efficacy of new medical products (drugs or medical devices), they must undergo a regulatory process known as qualification. While in the USA the FDA provides a regulatory pathway for the qualification of predictive models as device development tools, in Europe such pathway is not defined yet, primarily because of the lack of an appropriate harmonised standard.
The development of new harmonised standards is a complex and time-consuming process. Currently, there is no technical standard in the EU regulatory system that can be used to demonstrate the credibility of an in silico trials solution, which the American Society of Mechanical Engineers Verification & Validation 40 (ASME VV-40) provides.
Another issue is the lack in the EU regulatory system for medical devices of a process equivalent to the qualification advice procedure provided by the European Medicine Agency for new methodologies used in the development and derisking of new medicinal products. Such process allows developers of in silico methodologies to obtain the approval of the regulator, which allows them to use it in any medical device certification submission, without any further scrutiny of the in silico methodology.
It is important to pursue globally accepted standards that provide each regulator the necessary technical level upon which to evaluate the credibility of the In Silico Trials used in producing regulatory evidence. It is thus necessary, to develop an International Organization for Standardization (ISO) standard that is recognised by FDA and harmonised in the EU regulatory system, to evaluate the credibility of In Silico Trials technologies.
The aim of the position paper is to propose a possible trajectory for a wider adoption of In Silico Trials solutions in the CE Marking system for medical devices, which will definitely provide specific benefits to stakeholders. The In Silico World Community of Practice conducted a consultation and provided a list of the expectation of the main benefits of the various stakeholders (as manufacturers, health system and policy makers and patients).
In silico trials methodologies will play a growing and fundamental role in the development and de-risking of new medical devices in the future. The European regulatory system must embrace and guide this revolution, in order to limit distorted quality by different internal processes within notified bodies and also avoid 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.
To learn more about this topic, read the full paper HERE.