Design and development of novel reactors for manufacturing PEGylated biopharmaceuticals

用于制造聚乙二醇化生物制药的新型反应器的设计和开发

• 批准号: 526374-2018
• 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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=651805
• 关键词: Design; development; novel; reactors; manufacturing

Life-saving protein biopharmaceuticals such as monoclonal antibodies and vaccines are increasingly being used**for a range of therapeutic applications. These are usually delivered in the form of injections. Formulating such**products is challenging due to major problems such as immunogenicity and short in-vivo half-life, and stability**issues such as susceptibility to degradation, chemical modification, denaturation and aggregation. Most of these**issues could be addressed by PEGylation which involves the covalent attachment of the synthetic polymer**polyethylene glycol (or PEG) to the protein molecule. BioVectra is a Prince Edward Island based company**with an established track record in manufacturing reagents used for protein PEGylation. However, current**PEGylation processes result in significant by-product synthesis, resulting in lower product recovery and**increased production cost. The proposed work addresses an urgent need expressed by our industrial partner,**BioVectra, i.e. improvement in efficiency of manufacturing PEGylated biopharmaceuticals. We propose to**address this challenge through the design and development of novel and efficient reactors for protein**PEGylation. We have a proven track record in designing and developing novel devices for conducting chemical**reactions and separations. The main attributes of the robust reactors developed in our group include superior**hydraulics, narrow residence time distribution, minimal back-mixing and uniform superficial velocities, all of**which will contribute towards increasing efficiency of protein PEGylation. Improvement in manufacturing**efficiency through the development of the novel reactor systems will increase product recovery, lower**manufacturing cost, and make the product safe for use. Consequently, life-saving medicine for the treatment of**serious diseases would become more affordable and accessible to the Canadian healthcare system. HQP trained**in this project would also be able to join the Canadian workforce and make valuable contributions to the**Canadian economy.

拯救生命的蛋白质生物药物，如单克隆抗体和疫苗，正越来越多地用于 ** 一系列的治疗应用。这些通常以注射剂的形式提供。由于存在免疫原性和体内半衰期短等主要问题以及易降解、化学修饰、变性和聚集等稳定性问题，因此配制此类 ** 产品具有挑战性。这些问题中的大多数可以通过聚乙二醇化来解决，聚乙二醇化涉及合成聚合物聚乙二醇（或PEG）与蛋白质分子的共价连接。BioVectra是一家位于爱德华王子岛的公司 **，在蛋白质聚乙二醇化试剂的生产方面拥有良好的记录。然而，目前的 ** PEG化方法导致大量的副产物合成，导致较低的产物回收率和 ** 增加的生产成本。拟议的工作解决了我们的工业合作伙伴BioVectra表达的迫切需求，即提高聚乙二醇化生物制药的生产效率。我们建议通过设计和开发新型高效的蛋白质聚乙二醇化反应器来应对这一挑战。我们在设计和开发用于进行化学反应和分离的新型设备方面有着良好的记录。我们小组开发的耐用反应器的主要属性包括上级 ** 水力学、窄停留时间分布、最小返混和均匀表观速度，所有这些 ** 都将有助于提高蛋白质聚乙二醇化的效率。通过开发新型反应器系统来提高生产效率，将增加产品回收率，降低生产成本，并使产品使用安全。因此，治疗 ** 严重疾病的救生药物将变得更加负担得起，加拿大保健系统也更容易获得。在这个项目中培训的HQP也将能够加入加拿大的劳动力队伍，为加拿大的经济做出宝贵的贡献。