Periodic Reporting for period 2 - ISW (In Silico World: Lowering barriers to ubiquitous adoption of In Silico Trials)
Période du rapport: 2022-07-01 au 2023-12-31
The ISW consortium aims to lower the main barriers preventing a faster uptake of In Silico Trials. The six project’s objects are:
• O1 - Better models
• O2 - Validation collections
• O3 - Technical standards and regulatory barriers
• O4 - Responsible Research & Innovation
• O5 - Scalability and efficient computing
• O1 - Better models
• O2 - Validation collections
• O3 - Technical standards and regulatory barriers
• O4 - Responsible Research & Innovation
• O5 - Scalability and efficient computing
The In Silico World (ISW) project is running to date on time, on specifications, and with the planned resources.
We developed or further developed 11 solutions for “In Silico Trials” (IST), intended as the use of computer modelling and simulation to develop new medical products and assess their safety and efficacy. These cover medical devices, drugs, and even advanced medicinal products for regenerative medicine to treat various diseases, from osteoporosis to multiple sclerosis.
To date, we have released three data collections in Open Access designed to make the validation and the cross-comparison of specific In Silico Trial solutions easier; three more are in preparation. This will allow the research community to develop better IST solutions faster.
A major barrier to the adoption of ISTs is the regulatory one. The ISW consortium facilitated a conversation between IEC and ISO (the two standardisation bodies whose standards can be harmonised in the EU system) with the ASME, the USA standardisation body responsible for the VV-40 standard at the basis of the American regulatory pathway for models’ credibility. This recently created an IEC/ISO workgroup to develop a standard similar to the VV-40, enabling such pathways in the EU. And in the meantime, EU notified bodies will have to accept evidence based on the VV-40.
We also coordinated a large international group of experts who collaboratively wrote the first book on the so-called Good Simulation Practice, which is the best practice for modelling and simulation in developing new medical products. Nature Springer will publish The book as Open Access in March 2024.
Last, we conducted two qualification advice procedures with the European Medicine Agency on possibly using two IST solutions as drug development tools. The second advice produced a letter of support by the agency, but more importantly, it allowed to bring to light the profound cultural differences between our research community and that of pharmacology regulators on the role of computer models as possible alternatives to animal and human experimentation. A full report of this experience will be published in Open Access in April 2024, with a copy of all the documentation produced during these two qualification advice procedures.
The ISW consortium has also produced a Policy Brief and legal and ethical inventory on IST, providing useful resources to other stakeholders in our community.
Concerning the barrier of a workforce not yet trained in the development and use of IST, we have now developed several full curricula for the training and re-training of such workforce, identifying for each profile the necessary Intended Learning Outcomes and the detailed curriculum. We are now producing educational materials that will make it easier for European Universities and companies to deliver training on In Silico Trials.
For all 11 IST solutions, we defined regulatory and exploitation pathways. Two of these solutions are now commercially available through partner In Silico Trial Technologies; one is provided as part of their consulting services to the pharma industry by partner Mimesis, and one should soon become a service solution by partner Materialise. In doing this, we explored different possible business models to exploit this type of technology commercially.
We developed or further developed 11 solutions for “In Silico Trials” (IST), intended as the use of computer modelling and simulation to develop new medical products and assess their safety and efficacy. These cover medical devices, drugs, and even advanced medicinal products for regenerative medicine to treat various diseases, from osteoporosis to multiple sclerosis.
To date, we have released three data collections in Open Access designed to make the validation and the cross-comparison of specific In Silico Trial solutions easier; three more are in preparation. This will allow the research community to develop better IST solutions faster.
A major barrier to the adoption of ISTs is the regulatory one. The ISW consortium facilitated a conversation between IEC and ISO (the two standardisation bodies whose standards can be harmonised in the EU system) with the ASME, the USA standardisation body responsible for the VV-40 standard at the basis of the American regulatory pathway for models’ credibility. This recently created an IEC/ISO workgroup to develop a standard similar to the VV-40, enabling such pathways in the EU. And in the meantime, EU notified bodies will have to accept evidence based on the VV-40.
We also coordinated a large international group of experts who collaboratively wrote the first book on the so-called Good Simulation Practice, which is the best practice for modelling and simulation in developing new medical products. Nature Springer will publish The book as Open Access in March 2024.
Last, we conducted two qualification advice procedures with the European Medicine Agency on possibly using two IST solutions as drug development tools. The second advice produced a letter of support by the agency, but more importantly, it allowed to bring to light the profound cultural differences between our research community and that of pharmacology regulators on the role of computer models as possible alternatives to animal and human experimentation. A full report of this experience will be published in Open Access in April 2024, with a copy of all the documentation produced during these two qualification advice procedures.
The ISW consortium has also produced a Policy Brief and legal and ethical inventory on IST, providing useful resources to other stakeholders in our community.
Concerning the barrier of a workforce not yet trained in the development and use of IST, we have now developed several full curricula for the training and re-training of such workforce, identifying for each profile the necessary Intended Learning Outcomes and the detailed curriculum. We are now producing educational materials that will make it easier for European Universities and companies to deliver training on In Silico Trials.
For all 11 IST solutions, we defined regulatory and exploitation pathways. Two of these solutions are now commercially available through partner In Silico Trial Technologies; one is provided as part of their consulting services to the pharma industry by partner Mimesis, and one should soon become a service solution by partner Materialise. In doing this, we explored different possible business models to exploit this type of technology commercially.
The In Silico World project aims to accelerate the uptake of modelling and simulation technologies for the development and regulatory assessment of medicines and medical devices (hereinafter referred generically as in silico trials technologies) by developing innovative solutions that address the main barriers to their uptake. Eventually, In Silico World will speed up the uptake of in silico testing, increase the trust in these innovative technologies by the main stakeholders, change the design of regulatory trials to include in silico technologies, and consolidate the regulatory pathways based on in silico trials. The long-term impact will be reducing the costs and duration of developing a regulatory assessment of new medical products while maintaining or improving the level of safety provided by conventional approaches.