Senior Consultant and Lead Software Development esqlabs GmbH Munich, Bayern, Germany
Background: The integration of complex mechanism-based quantitative systems pharmacology (QSP) models into physiologically based pharmacokinetics (PBPK) modeling frameworks leads to an ever-increasing model complexity. Maintenance and extension of such platforms become challenging and error prone. The complexity of the integration of such models limits their life cycle and distribution in the scientific community. Regulatory bodies increasingly demand the qualification of all intended use scenarios of modeling platforms. Considering the above-mentioned complexity, new technical approaches for automated qualification and exchangeability of sub-models are required. Methods: The Open Systems Pharmacology Suite (www.open-systems-pharmacology.org) is an open-source modeling and simulation software used in life sciences applications for PBPK and QSP modeling. The software is particularly well suited for the integration of complex QSP models with the PBPK framework. The open source community is encouraged to publish their models to drive pre-competitive open science forward. A modularization and automated re-qualification framework for the software is being implemented to address the above-discussed challenges. Results: The new version of the QSP modeling tool MoBi organizes a modeling project in modules. A module can be a full PBPK model, an extension of the default PBPK backbone (eg a new organ or administration site), an effect or a disease module. By combining modules, the user can create simulations with different individuals, medications, disease states, and level of detail required for a particular use case. The modules can be distributed separately and reused in different projects. The modularization concept allows the implementation of the automated re-qualification framework. The framework supports report generation for separate modules and whole platforms for specified application scenarios. Conclusion: The integrated qualification framework allows continuous quality control, qualification, and deployment of complex PB-QSP models and will support the use of PB effects modeling for regulatory submissions. The modular concept simplifies the process of model exchange and integration into existing projects, facilitating the reusability of modeling activities and promoting exchange within an open science community.
