Technology-enhanced biopharmaceuticals discovery and manufacturing (TBioDM)

全球制药行业正处于一个根本性的转变时期，从主要的小分子药物迅速转向生物大分子（生物制药）。例如，如今赛诺菲巴斯德72%的研发项目是生物制药。“发现阶段”过程——确定候选分子是否表现出目标相互作用——在很大程度上适应了这种转变，然而，这只会加剧一个新出现的问题：从根本上说，生物大分子的表征比小分子药物更具挑战性，因此，当早期候选药物被确定时，基于对候选药物、其络合特性及其对生命系统的影响的彻底了解，为进一步开发提供基本原理是极其困难的。这种“表征差距”是生物制药开发中的一个关键瓶颈，即已知候选药物表现出所需的相互作用，但对相互作用的性质（甚至通常是候选药物本身）一无所知。对于必须根据有限的生物分析数据做出发展决策的制药公司来说，这也是一个重大风险。约克大学（York University）研究的新技术正在出现，可能会缩小表征上的差距。这些工具包括能够快速，详细的结构和构象稳定性分析，结合相互作用的定量测量和生物药物对生命系统影响的综合确定。拟议的研究旨在开发和适应这些独特的工具，以表征工业工作流程中的“现实世界”生物制药。该项目结合了约克大学的技术和专业知识，赛诺菲巴斯德的生物制药以及Sciex和Fluidigm加拿大公司的尖端分析平台，为生物制药开发中的“表征差距”瓶颈提供了完整的解决方案。

The global pharmaceuticals industry is in a period of fundamental transition, moving rapidly from predominantly small molecule drugs to biological macromolecules (biopharmaceuticals). Today, for instance, 72% of Sanofi Pasteur's research and development projects are biopharmaceuticals. 'Discovery Phase' processes - in which it is determined if candidate molecules exhibit a target interaction - have largely adapted to this shift, however, this has only exacerbated an emerging problem: Biological macromolecules are fundamentally more challenging to characterize than small molecule drugs, so that when early-stage candidates are identified, it is exceedingly difficult to provide a rationale for further development based on a thorough understanding of the candidate, its complexation characteristics and its effect on living systems. This 'characterization gap', in which candidates are known to exhibit the desired interaction but nothing is known about the nature of the interaction (or often even the candidate itself), is a critical bottleneck in biopharmaceuticals development. It is also a significant risk to pharmaceutical companies who must make advancement decisions based on limited bioanalytical data. New technologies are emerging from research at York University that could close the characterization gap. These include tools capable of rapid, detailed structure and conformational stability analyses, quantitative measurements of binding interactions and comprehensive determinations of biopharmaceutical effects on living systems. The proposed research is aimed at the development and adaptation of these unique tools for characterization of 'real-world' biopharmaceuticals in industrial workflows. The program combines technologies and expertise from York, biopharmaceuticals from Sanofi Pasteur and cutting-edge analytical platforms from Sciex and Fluidigm Canada to deliver a complete solution to the 'characterization gap' bottleneck in biopharmaceuticals development.