Real time flux modelling in biopharmaceutical bioprocessing

生物制药生物加工中的实时通量建模

• 批准号: BB/I010386/1
• 负责人: Brian McNeil
• 金额: $ 12.54万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI010386%2F1
• 关键词: Real; time; flux; modelling; biopharmaceutical

Biopharmaceuticals, such as herceptin (trastumazab) which is used in breast cancer treatment, have revolutionised the treatment of many serious diseases, such as solid tumours, leukaemias, degenerative illnesses such as Alzheimer's, and other diseases having complex contributors, such as asthma. However, in addition to being the most potent drugs humanity has ever deployed, these are also the most complex. This implies lengthy development cycles, and very high costs for therapy. A course of herceptin treatment costs around £27,000 per patient. This has led to serious concerns over access to, and availability of these potent drugs. In order to make these complex agents, specially developed (genetically altered) microbial or animal cell systems (expression systems) are cultured in fermenters or bioreactors. But our understanding of how the interaction of the genetic alterations we introduce, and the fermenter or bioreactor environment we culture the cells within, impact upon the cell metabolism is quite limited, especially in early development phase. This lack of clear knowledge about cell metabolism is one major cause of the long, costly drug development cycle of these agents. Our approach is to focus cutting edge techniques upon achieving better undertsanding of the behaviour of these expression systems early in the development phase. We plan to use non-invasive monitoring techniques (near and mid infrared spectroscopies) actually in the culture vessels together with a previously non real time metabolic analysis tool (flux balancing) to gain real time understanding of the metabolism of these specialised cells when in culture. This technology would give increased knowledge of cell metabolism early in the process cycle, helping accelerate product development, leading to reduced cost therapeutics reaching patients more speedily. This would contribute to increased health in society in general. It would also provide a competitive advantage to the UK biomanuafturing sector involved in making these drugs. In the very near future, this approach could greatly help the development and deployment of specialised cell based therapies ( e.g. stem cells). This is especially important as these agents are even more complex than biopharmaceuticals, and have tremendous potential to contribute to enhancing the health and welfare of society in the immediate future. Achieving

生物制药，如用于乳腺癌治疗的赫赛汀（曲妥珠单抗），已经彻底改变了许多严重疾病的治疗，如实体瘤、白血病、阿尔茨海默氏症等退行性疾病，以及其他病因复杂的疾病，如哮喘。然而，这些药物除了是人类有史以来使用过的最有效的药物之外，也是最复杂的药物。这意味着漫长的开发周期和非常高的治疗费用。一个疗程的赫赛汀治疗费用约为每位患者2.7万英镑。这导致了对这些强效药物的获取和可得性的严重关切。为了制造这些复杂的制剂，在发酵罐或生物反应器中培养专门开发的（基因改变的）微生物或动物细胞系统（表达系统）。但是我们对我们引入的基因改变如何相互作用的理解，以及我们培养细胞的发酵罐或生物反应器环境，对细胞代谢的影响是相当有限的，特别是在早期发育阶段。缺乏对细胞代谢的清晰认识是这些药物开发周期长、成本高的一个主要原因。我们的方法是专注于在开发阶段早期更好地理解这些表达系统的行为的尖端技术。我们计划在培养容器中使用非侵入性监测技术（近红外和中红外光谱）以及以前的非实时代谢分析工具（通量平衡）来实时了解这些特化细胞在培养过程中的代谢情况。这项技术将在过程周期的早期增加对细胞代谢的了解，有助于加速产品开发，从而使成本更低的治疗药物更快地到达患者手中。这将有助于提高整个社会的健康水平。它还将为参与制造这些药物的英国生物制造部门提供竞争优势。在不久的将来，这种方法可以极大地帮助开发和部署专门的基于细胞的疗法（例如干细胞）。这一点尤其重要，因为这些制剂甚至比生物制药更复杂，在不久的将来有巨大的潜力为增进社会的健康和福利作出贡献。实现

项目成果

PAT Applied in Biopharmaceutical Process Development and Manufacturing: An Enabling Tool for Quality-by-design

PAT 在生物制药工艺开发和制造中的应用：质量源于设计的支持工具

• 发表时间: 2011
• 作者: Undey, Cenk;Low, Duncan;Menezes, Jose C.;Koch, Mel
• 通讯作者: Koch, Mel

Towards better understanding of an industrial cell factory: investigating the feasibility of real-time metabolic flux analysis in Pichia pastoris.

• DOI: 10.1186/1475-2859-12-51
• 发表时间: 2013-05-21
• 期刊: Microbial cell factories
• 影响因子: 6.4
• 作者: Fazenda ML;Dias JM;Harvey LM;Nordon A;Edrada-Ebel R;Littlejohn D;McNeil B
• 通讯作者: McNeil B