A State-of-the-Art Virtual Bioequivalence Platform and Case Studies on Complex Formulations, Systemic and Local Concentration-based Bioequivalence

最先进的虚拟生物等效性平台以及复杂制剂、基于全身和局部浓度的生物等效性案例研究

• 批准号: 10788932
• 负责人: Frederic Bois
• 金额: $ 25万
• 依托单位: CERTARA UK LIMITED
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-03 至 2025-07-02
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10788932
• 关键词: State; Art; Virtual; Bioequivalence; Platform

Project Summary/ Abstract In the field of biopharmaceutics, virtual bioequivalence (VBE) trial simulations have the potential to increase the speed of drug development, lower its cost and reduce exposure of human volunteers and patients to unneeded therapies. VBE is based on the proven ability of mechanistic physiologically-based pharmacokinetic (PBPK) models to simulate realistic virtual cohorts of patients which can replace full clinical trials. However, well-defined and verified workflows and examples of VBE applications are not yet fully established. Having well-defined workflows in a seamless, user- friendly, and widely accessible modeling platform tested with multiple case studies will ensure a wider adoption VBE by industry and regulatory bodies. This project proposes to develop an integrated VBE platform yielding optimal decisions for a matter directly related to the health and safety of patients, and their optimal and cost-effective treatment. The capacity to integrate various streams of data (in vitro information on drug and formulations, physiological knowledge of what conditions the ability of a drug to reach its site of action, variability physiology and metabolism across patients) is not just a software production exercise but requires deep knowledge of each area and expertise in the field. This needs to be complemented by rigorous statistical analyses, as applied to real clinical data, of the VBE simulations. Our overall objectives are to • Develop a software platform allowing for flexible, fit-for-purpose, VBE workflows taking advantage of existing tools and adding user-defined modules. • Provide guidance on VBE workflow design (how to solve particular questions, pitfalls to avoid, help with the design of supporting experiments and trials) for regulatory agencies/industries. • Make maximum use of the capabilities of existing in vitro data analysis and modeling tools to extract key parameters values relevant to formulation differences for selected routes of administration (e.g., oral, intra-muscular injection). • Conduct six in-depth VBE case studies, very close to real life cases, where individualized BE clinical data are available to the team through literature reports or internal investigations; Experimental in vitro data is already available or will be generated as required. • Create automated default reporting templates that clearly document the workflow and its results and are easily understood by non-users for assessment purpose (with flexibility to modify default templates when needed). Our specific aims are divided in workflow design, software implementation and case studies. We anticipate that the proposed research will result in a wider patient centric application of population PBPK models in generic drug development and regulatory reviews, but also for innovators’ drugs, enhancing drug efficacy, availability and safety for all the world’s population.

项目摘要/摘要 在生物制药领域，虚拟生物等效性（VBE）试验模拟有可能 提高药物开发的速度，降低其成本并减少人类志愿者的暴露 和患者进行不需要的疗法。 VBE基于机械的可靠能力 基于生理的药代动力学（PBPK）模型，以模拟现实的虚拟人群 可以取代完整的临床试验。但是，定义明确且经过验证的工作流以及 VBE应用程序尚未完全确定。在无缝的，用户 - 通过多个案例研究测试的友好且广泛访问的建模平台将确保 行业和监管机构的广泛采用。这个项目的提议要开发 集成的VBE平台为与健康直接相关的问题提供最佳决策 患者的安全及其最佳且具有成本效益的治疗。整合各种的能力 数据流（有关药物和公式的体外信息，物理知识 条件药物达到其作用部位，可变性生理和代谢的能力 跨患者）不仅是软件生产练习，还需要深入了解每个领域 和该领域的专业知识。这需要通过严格的统计分析来完成 到实际临床数据，VBE模拟。我们的整体目标是 •开发一个软件平台，允许灵活，合身的用途，VBE工作流程 现有工具的优势并添加用户定义的模块。 •提供有关VBE工作流程设计的指导（如何解决特定问题，陷阱以避免， 帮助设计支持实验和试验的监管机构/行业的试验。 •最大程度地利用现有的体外数据分析和建模工具的功能 提取关键参数值与制定选定路由的差异相关的值 给药（例如口服，肌肉内注射）。 •进行六个深入的VBE案例研究，非常接近现实生活中的案例， 团队可以通过文献报告或内部调查提供临床数据； 实验性的体外数据已经可用或根据需要生成。 •创建自动默认报告模板，清楚地记录了工作流及其其ITS 结果，非用户很容易理解评估目的（具有灵活性 在需要时修改默认模板）。 我们的具体目标在工作流程设计，软件实施和案例研究中分为。我们 预计拟议的研究将导致更广泛的以患者为中心的人口 PBPK通用药物开发和监管审查中的模型，也用于创新者的药物， 提高全世界人口的药物效率，可用性和安全性。