Design and development of novel reactors for manufacturing PEGylated biopharmaceuticals

拯救生命的蛋白质生物制药，如单抗和疫苗，正越来越多地被用于**一系列治疗应用。这些通常是以注射的形式提供的。由于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，研制此类**产品具有挑战性。这些问题中的大多数都可以通过聚乙二醇化来解决，聚乙二醇化涉及到合成聚合物聚乙二醇(或聚乙二醇组分)与蛋白质分子的共价连接。BioVectra是一家总部位于爱德华王子岛的公司**，在生产用于蛋白质聚乙二醇化的试剂方面有着良好的记录。然而，目前的**聚乙二醇化工艺导致大量副产物合成，导致产品回收率较低，**增加了生产成本。拟议的工作满足了我们的工业合作伙伴BioVectra表达的一个迫切需求，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用于蛋白质聚乙二醇化的新型高效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。我们团队开发的坚固耐用的反应器的主要属性包括优越的水力**、窄的停留时间分布、最小的返混和均匀的表观速度，所有这些**都将有助于提高蛋白质聚乙二醇化的效率。通过开发新型反应堆系统提高制造效率，将提高产品回收率，降低制造成本，并使产品可以安全使用。因此，用于治疗**严重疾病的救命药物将变得更加负担得起，加拿大医疗体系也更容易获得。受过这个项目培训的HQP也将能够加入加拿大的劳动力大军，并为**加拿大经济做出宝贵的贡献。

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.