Manufacturing Process Development for Bioengineered FVIII

生物工程 FVIII 的制造工艺开发

基本信息

批准号：
8454386
负责人：
Gabriela Denning
金额：
$ 38.64万
依托单位：
EXPRESSION THERAPEUTICS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8454386
关键词：
Adolescence Anabolism Animals Biological Products Biomanufacturing Biomedical Engineering Bioreactors Blood Capital Cell Culture Techniques Cell Density Cell Line Cells Chromatography Collection Column Chromatography Complex Conditioned Culture Media Development Disease Drug Formulations Endoplasmic Reticulum Factor VIII Fermentation Funding Goals Golgi Apparatus Growth Hamsters Harvest Health Services Accessibility Hemophilia A Intellectual Property Investigational New Drug Application Ion Exchange Kidney Kilogram Laboratories Legal patent Mammalian Cell Marketing Methods Patients Perfusion Persons Pharmaceutical Preparations Pharmacologic Substance Pharmacy facility Phase Price Procedures Process Production Productivity Proteins Qualifying Recombinant Proteins Recombinants Replacement Therapy Resources Running Serum Small Business Innovation Research Grant Suspension substance Suspensions System Technology Therapeutic Transgenes Validation base blood product cost cost effective density design efficacy testing good laboratory practice human F8 protein improved instrumentation manufacturing process manufacturing process development method development mortality novel pre-clinical preclinical efficacy preclinical safety public health relevance recombinant antihemophilic factor VIII response safety testing scale up stability testing

项目摘要

DESCRIPTION (provided by applicant): The manufacturing of recombinant coagulation factor VIII is a complex, labor and capital intensive endeavor. Of the recombinant proteins currently marketed, coagulation factor VIII is manufactured with the lowest efficiency and is by far the most expensive on a per unit mass basis with a pharmacy price of $10,000,000 per gram. The goal of the current application is to develop a product technology and a manufacturing process that can improve the production volume and pharmacy price of factor VIII biologics. Expression Therapeutics has developed two technologies, a bioengineered factor VIII transgene that demonstrates 100-fold greater expression than standard human factor VIII, and a new baby hamster kidney-derived (BHK) cell line, designated BHK-MS, that can be cultured and expanded indefinitely and at high density in serum and blood product-free medium under suspension bioreactor conditions. In the current application, we propose to optimize the fermentation and purification processes and conduct a scaled up production run that will demonstrate proof of concept of the manufacturing process and generate a substantial supply of bulk drug substance qualified for subsequent preclinical safety, efficacy and stability testing necessary to submit an Investigational New Drug application during phase II of the SBIR mechanism.

描述（由申请人提供）：重组凝血因子 VIII 的生产是一项复杂的、劳动力和资本密集型的工作。在目前市售的重组蛋白中，凝血因子 VIII 的生产效率最低，并且按单位质量计算是迄今为止最昂贵的，其药房价格为每克 10,000,000 美元。目前申请的目标是开发一种能够提高VIII因子生物制剂产量和药价的产品技术和制造工艺。 Expression Therapeutics 开发了两项技术，一种是生物工程因子 VIII 转基因，其表达量比标准人类因子 VIII 高 100 倍；另一种是新的幼仓鼠肾源性 (BHK) 细胞系，命名为 BHK-MS，可培养和扩增在悬浮生物反应器条件下，在无血清和血液制品的培养基中无限期且高密度。在当前的应用中，我们建议优化发酵和纯化工艺，并进行规模化生产运行，以证明制造工艺的概念验证，并产生大量符合后续临床前安全性、有效性和稳定性测试资格的原料药供应。有必要在 SBIR 机制第二阶段提交研究性新药申请。