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Model-based development and scale-up of chromatographic separation processes

基于模型的色谱分离过程开发和放大

基本信息

批准号：
453248-2013
负责人：
Ghosh, Raja
金额：
$ 1.82万
依托单位：
McMaster University
依托单位国家：
加拿大
项目类别：
Engage Grants Program
财政年份：
2013
资助国家：
加拿大
起止时间：
2013-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=541372
关键词：
Model based development scale up

项目摘要

Biopharmaceutical products such as monoclonal antibodies, enzymes and interferons are increasingly being added to the repertoire of life saving drugs available to physicians for treating life-threatening ailments such as cancer, cardiac diseases and viral infections. As with other pharmaceutical products, these need to be available in highly pure form for their intended therapeutic applications. Biopharmaceuticals are very expensive due to a combination of factors such as high development and manufacturing cost, and relatively low shelf-life. For a typical product such as a monoclonal antibody, purification cost accounts for almost 60-80% of the total manufacturing cost. Most biopharmaceuticals are purified using column or membrane-based chromatography. While chromatography is widely used in the industry, it is quite difficult to scale-up. This is due to the fact that any chromatographic separation involves the complex interplay between adsorption (i.e. thermodynamics) and mass transport of material (i.e. kinetics). Improperly scaled-up processes can be extremely inefficient and this can have a detrimental effect on process economics. The objective of this project is to understand the thermodynamic and kinetic contributions in chromatographic purification of biopharmaceuticals such as monoclonal antibodies. Based on an understanding of these individual contributing factors, models for scale-up of chromatographic purification processes for these products will be developed. Such models will be useful in designing and developing cost-effective purification processes and thereby increase manufacturing efficiency in the biopharmaceutical industry.

生物制药产品，如单克隆抗体，酶和干扰素越来越多地被添加到医生可用于治疗危及生命的疾病，如癌症，心脏病和病毒感染的救生药物库。与其他药物产品一样，这些产品需要以高纯度的形式用于其预期的治疗应用。由于诸如高开发和制造成本以及相对低的保质期等因素的组合，生物药物非常昂贵。对于典型的产品如单克隆抗体，纯化成本几乎占总制造成本的60-80%。大多数生物制药是使用柱或膜基色谱纯化。虽然色谱法在工业中被广泛使用，但很难扩大规模。这是因为任何色谱分离都涉及吸附（即热力学）和物质传质（即动力学）之间的复杂相互作用。不适当地放大工艺可能效率极低，这可能对工艺经济性产生不利影响。本计画的目的是了解生物制药如单克隆抗体的层析纯化中热力学与动力学的贡献。基于对这些单个影响因素的理解，将开发这些产品的色谱纯化工艺放大模型。这种模型将有助于设计和开发具有成本效益的纯化工艺，从而提高生物制药行业的生产效率。