CEC03-05 Integrated PBPK/QST modeling to inform the safety assessmentpractical hands-on examples across multiple disease areas

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters Pub Date : 2025-09-01 DOI:10.1016/j.toxlet.2025.07.024

S. Schaller, P. Balazki

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引用次数: 0

Abstract

Building upon the foundational lectures on Physiologically Based Pharmacokinetic (PBPK) modeling and its integration with Quantitative Systems Toxicology (QST), this final session culminates in a practical demonstration of an advanced, modular approach to safety assessment. We will introduce the concept of a “Quantitative Ecosystem” designed for Next Generation Risk Assessment (NGRA). This ecosystem leverages modular PBPK-QST platforms, exemplified by the open-source Open Systems Pharmacology (OSP) Suite (www.open-systems-pharmacology.org ^[1]), to enhance and streamline toxicological evaluations.

This presentation will feature a software demonstration focusing on how the OSP Suite facilitates this integrated and modular ecosystem. You will see how it supports the seamless development, validation, and deployment of PBPK and QST models tailored for safety applications. We will illustrate its power through practical, hands-on examples relevant to NGRA, including:

•
A Thyroid PBPK-QST/quantitative Adverse Outcome Pathway (qAOP) platform for the risk assessment of thyroid disruptors.
•
A DILI (Drug-Induced Liver Injury) platform designed to assess and predict potential liver injury.

The session will highlight how key features of the OSP Suite, such as its continuously evolving model libraries (PK-Sim for PBPK, MoBi for QST modules), model modularity, reusability, and pathways towards automated qualification, contribute to more robust, transparent, reproducible, and efficient safety decision-making. This demonstration will directly complement and set the stage for the hands-on exercises where participants will utilize the OSP software to explore model parameterization and predict safety risks.

Learning Objectives for this Presentation:

Upon completion of this session, participants will be able to:

•
Understand the “Quantitative Ecosystem” concept and its application to modular PBPK-QST in safety and Next Generation Risk Assessment.
•
Recognize how the Open Systems Pharmacology (OSP) Suite and its components (e.g., PK-Sim, MoBi) enable this modular and integrated approach.
•
Witness practical software applications for NGRA, specifically for assessing thyroid disruption and Drug-Induced Liver Injury.
•
Appreciate how modularity, model reusability, and features supporting automated qualification can enhance the robustness, transparency, and efficiency of safety evaluations.

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集成PBPK/QST模型，为跨多个疾病领域的安全评估提供实际操作示例

在基于生理的药代动力学（PBPK）建模及其与定量系统毒理学（QST）集成的基础讲座的基础上，最后一次会议以先进的模块化安全评估方法的实际演示为高潮。我们将引入为下一代风险评估（NGRA）设计的“定量生态系统”概念。该生态系统利用模块化PBPK-QST平台，以开源开放系统药理学（OSP）套件（www.open-systems-pharmacology.org[1]）为例，加强和简化毒理学评估。本次演讲将以软件演示为特色，重点介绍OSP套件如何促进这种集成和模块化生态系统。您将看到它如何支持为安全应用量身定制的PBPK和QST模型的无缝开发、验证和部署。我们将通过与NGRA相关的实际操作示例来说明其功能，包括：•用于甲状腺干扰物风险评估的甲状腺PBPK-QST/定量不良后果途径（qAOP）平台。•药物性肝损伤（DILI）平台，用于评估和预测潜在的肝损伤。会议将重点介绍OSP套件的关键特性，例如其不断发展的模型库（PBPK的PK-Sim， QST模块的MoBi），模型模块化，可重用性和自动化鉴定途径，如何有助于更强大，透明，可重复和高效的安全决策。该演示将直接补充并为实践练习奠定基础，参与者将利用OSP软件探索模型参数化并预测安全风险。学习目标：完成本课程后，学员将能够：•理解“定量生态系统”概念及其在安全和下一代风险评估模块化PBPK-QST中的应用。•认识开放系统药理学（OSP）套件及其组件（例如，PK-Sim, MoBi）如何实现这种模块化和集成方法。•见证NGRA的实际软件应用，特别是用于评估甲状腺紊乱和药物性肝损伤。•了解模块化、模型可重用性和支持自动化鉴定的特性如何增强安全评估的稳健性、透明度和效率。

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