The Virtual Human Platform for Safety Assessment (VHP4Safety) project: Next generation chemical safety assessment based on human data
Article Sidebar
Main Article Content
Abstract
The Virtual Human Platform for Safety Assessment (VHP4Safety) project aims to build a Virtual Human Platform (VHP) to protect human health and revolutionize the safety assessment of chemicals and pharmaceuticals by transitioning from animal-based to human-based approaches. The goal of this article is to introduce the project and its interdisciplinary approach to co-creation with multiple academic, regulatory, industrial and societal partners covering the entire safety assessment knowledge chain. Three research lines drive the project: 1) building the VHP; 2) feeding the VHP with human data; and 3) implementing the VHP. The project focusses on three case studies that incorporate human relevant scenarios not included in current animal-based safety assessment strategies. The VHP is built on tools and services, including pharmacokinetic and computational models, and integrates several data sources within each case study, including data on human physiology, epidemiology, toxicokinetic and -dynamic parameters, as well as data on chemical characteristics and exposures. In addition, the VHP integrates new data generated within the project using new approach methodologies representing key events within adverse outcome pathways. Implementation of the VHP is investigated using an innovation systems approach, engaging stakeholders and organizing training and education. Central to the VHP4Safety project is our co-creative approach, which facilitated by biannual designathons and hackathons that foster active involvement of all project participants from over 30 partner organizations. By integrating technological innovations with transparency and stakeholder collaboration, the VHP4Safety project will help shape the transition to the next generation safety assessment in which animal testing becomes redundant.
Plain language summary
The Virtual Human Platform for Safety Assessment (VHP4Safety) project will build a virtual human platform (VHP) to determine the safety of chemicals and pharmaceuticals for human health based solely on human biology. By integrating innovations in data science, new approach methodologies and transition science, the VHP4Safety project will help shape the transition to safety assessment in which animal testing becomes redundant. This goal of this article is to introduce the project and its interdisciplinary approach to co-creation with multiple academic, regulatory, industrial and societal partners covering the entire safety assessment knowledge chain. We invite stakeholders who support our vision to collaborate and provide input, in order to enhance transparency and acceptance of the VHP in next generation safety assessment based on human data.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Articles are distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited (CC-BY). Copyright on any article in ALTEX is retained by the author(s).
Bacall, F., Apaolaza, A., Andrabi, M. et al. (2023). Making bioinformatics training events and material more discoverable using tess, the elixir training portal. Curr Protoc 3, e682. doi:10.1002/cpz1.682
Callegaro, G., Kunnen, S. J., Trairatphisan, P. et al. (2021). The human hepatocyte TXG-MAPr: Gene co-expression network modules to support mechanism-based risk assessment. Arch Toxicol 95, 3745-3775. doi:10.1007/s00204-021-03141-w
de Jong, S. P. L. and Balaban, C. (2022). How universities influence societal impact practices: Academics’ sense-making of organizational impact strategies. Science and Public Policy 49, 609-620. doi:10.1093/scipol/scac012
Ducray, A. D., Wiedmer, L., Herren, F. et al. (2020). Quantitative characterization of phenotypical markers after differentiation of sh-sy5y cells. CNS Neurol Disord Drug Targets 19, 618-629. doi:10.2174/1871527319666200708132716
EC - European Commission: Joint Research Centre, Barroso, J., Batista Leite, S. et al. (2023). Non-animal methods in science and regulation: EURL ECVAM status report 2022. Publications Office of the European Union. https://data.europa.eu/doi/10.2760/500414
Harrow, J., Drysdale, R., Smith, A. et al. (2021). Elixir: Providing a sustainable infrastructure for life science data at european scale. Bioinformatics 37, 2506-2511. doi:10.1093/bioinformatics/btab481
Hekkert, M. P., Suurs, R. A. A., Negro, S. O. et al. (2007). Functions of innovation systems: A new approach for analysing technological change. Technological Forecasting and Social Change 74, 413-432. doi:10.1016/j.techfore.2006.03.002
Hekkert, M. P. and Negro, S. O. (2009). Functions of innovation systems as a framework to understand sustainable technological change: Empirical evidence for earlier claims. Technological Forecasting and Social Change 76, 584-594. doi:10.1016/j.techfore.2008.04.013
Jansen, J., van den Berge, B. T., van den Broek, M. et al. (2022). Human pluripotent stem cell-derived kidney organoids for personalized congenital and idiopathic nephrotic syndrome modeling. Development 149, doi:10.1242/dev.200198
Kooijman, M. (2013). Why animal studies are still being used in drug development. Altern Lab Anim 41, P79-81. doi:10.1177/026119291304100627
Kumar, K. K., Lowe, E. W., Jr., Aboud, A. A. et al. (2014). Cellular manganese content is developmentally regulated in human dopaminergic neurons. Sci Rep 4, 6801. doi:10.1038/srep06801
Martens, M., Stierum, R., Schymanski, E. L. et al. (2021). Elixir and toxicology: A community in development. F1000Res 10, doi:10.12688/f1000research.74502.2
Martens, M., Evelo, C. T. and Willighagen, E. L. (2022). Providing adverse outcome pathways from the aop-wiki in a semantic web format to increase usability and accessibility of the content. Appl In Vitro Toxicol 8, 2-13. doi:10.1089/aivt.2021.0010
Martens, M., Meuleman, A. B., Kearns, J. et al. (2023). Molecular adverse outcome pathways: Towards the implementation of transcriptomics data in risk assessments. bioRxiv 2023.2003.2002.530766. doi:10.1101/2023.03.02.530766
Meerman, J. J., Legler, J., Piersma, A. H. et al. (2023a). An adverse outcome pathway for chemical-induced parkinson's disease: Calcium is key. Neurotoxicology 99, 226-243. doi:10.1016/j.neuro.2023.11.001
Meerman, J. J., Wolterink, G., Hessel, E. V. S. et al. (2023b). Neurodegeneration in a regulatory context: The need for speed. Current Opinion in Toxicology 33, 100383. doi:10.1016/j.cotox.2022.100383
Piersma, A. H., van Benthem, J., Ezendam, J. and Kienhuis, A. S. (2018). Validation redefined. Toxicol In Vitro 46, 163-165. doi:10.1016/j.tiv.2017.10.013
Scholz, D., Pöltl, D., Genewsky, A. et al. (2011). Rapid, complete and large-scale generation of post-mitotic neurons from the human luhmes cell line. J Neurochem 119, 957-971. doi:10.1111/j.1471-4159.2011.07255.x
Schot, J. and Rip, A. (1997). The past and future of constructive technology assessment. Technological Forecasting and Social Change 54, 251-268. doi:10.1016/S0040-1625(96)00180-1
Schutgens, F., Rookmaaker, M. B., Margaritis, T. et al. (2019). Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nature Biotechnology 37, 303-313. doi:10.1038/s41587-019-0048-8
Smit, J. P. and Hessels, L. K. (2021). The production of scientific and societal value in research evaluation: A review of societal impact assessment methods. Research Evaluation 30, 323-335. doi:10.1093/reseval/rvab002
Tziva, M., Negro, S. O., Kalfagianni, A. and Hekkert, M. P. (2021). Alliances as system builders: On the conditions of network formation and system building in sustainability transitions. Journal of Cleaner Production 318, 128616. doi:10.1016/j.jclepro.2021.128616
Westmoreland, C., Bender, H. J., Doe, J. E. et al. (2022). Use of new approach methodologies (nams) in regulatory decisions for chemical safety: Report from an epaa deep dive workshop. Regul Toxicol Pharmacol 135, 105261. doi:10.1016/j.yrtph.2022.105261
Yousif, Z. K., Koola, J. D., Macedo, E. et al. (2023). Clinical characteristics and outcomes of drug-induced acute kidney injury cases. Kidney Int Rep 8, 2333-2344. doi:10.1016/j.ekir.2023.07.037