cGMP Manufacturing Platform for Biotherapeutics from Bioengineered Plants

描述(申请人提供)：使用生物工程植物制造生物制药产品提供了极大地降低成本的潜力，并创造了几乎无限供应的无病原体的重组蛋白质来源材料。然而，与任何重组蛋白质制造系统一样，必须严格建立每个生物工程植物系统的过程一致性，并必须确定过程中控制，以确保持续生产安全有效的药物。本研究的长期目标是建立一个符合当前良好制造规范(CGMP)要求的、具有良好特性的制造平台，以用于从生物工程马铃薯植物的叶片中低成本生产高质量、无病原体的重组蛋白。这项提案描述了基于申请人的创新方法进行的研究，这些方法使用严密监控的模块化生长室在明确的环境条件下生长和收获马铃薯植株的叶片，这些生长室可扩展以满足世界各地对许多已建立的和新兴的生物制药产品的医疗需求。在拟议研究的第一阶段，目标是描述模型生物工程马铃薯植株的生长特征，并监测重组蛋白表达在研究规模制造活动过程中在数量和质量(蛋白质结构和功能)方面的可测量变化。这项研究的结果将确定和建立过程中的监测参数，以评估收获的大宗产品的整体生产一致性。在这一阶段，预计成功的可能性很高，因为申请人已经很好地建立了在受控环境条件下生长马铃薯植株的稳健方法。此外，蓝鸟生物科学公司的M.Griffith博士拥有20年的生物制药产品开发专业知识，并在分离和鉴定用于治疗用途的重组和血浆衍生蛋白质方面拥有实际经验，他担任该项目的顾问，并制定了分析测试计划，以在制造活动期间记录模型蛋白质的结构和功能。根据这一信息，将提交第二阶段研究提案，以扩大生产活动，以获得足够的生物量，用于重组蛋白纯化和详细的生化特性。

DESCRIPTION (provided by applicant): The use of bioengineered plants for the manufacture of biopharmaceutical products offers the potential to dramatically lower the cost and to create an almost limitless supply of pathogen-free, recombinant protein source material. However, as with any recombinant protein manufacturing system, the process consistency of each bioengineered plant system must be rigorously established and in-process controls must be identified to ensure that safe and effective medicines will be consistently produced. The long-term objective of this research is to establish a well-characterized manufacturing platform that meets the requirements for current Good Manufacturing Practices (cGMP) that can be used for the low cost production of high quality, pathogen-free recombinant proteins from the foliage of bioengineered potato plants. This proposal describes studies that are based on the applicant's innovative methods for the growth and harvest of potato plant foliage under well-defined environmental conditions using closely monitored, modular, growth chambers that are scaleable to meet the worldwide medical need for many established and emerging biopharmaceutical products. During Phase I of the proposed research the objective is to characterize the growth of a model bioengineered potato plant and to monitor for measurable changes in recombinant protein expression, both in terms of quantity and quality (protein structure and function) over the course of a research scale manufacturing campaign. The results of this research will identify and establish in-process monitoring parameters to evaluate the overall production consistency of harvested bulk product. A high probability of success is expected during this phase because robust methods for the growth of potato plants under controlled environment conditions have been well established by the applicant. Further, Dr. M. Griffith of Bluebird Biosciences, Inc., who has two decades of biopharmaceutical product development expertise and hands on experience in the isolation and characterization of recombinant and plasma-derived proteins for therapeutic use, serves as a consultant to this project and has developed the analytical testing plan to document the structure and function of the model protein during the manufacturing campaign. Based on this information, a Phase II research proposal will be submitted to scale up the manufacturing campaign to obtain sufficient biomass for recombinant protein purification and detailed biochemical characterization.