cGMP Manufacturing Platform for Biotherapeutics from Bioengineered Plants

描述（由申请人提供）：使用生物工程植物生产生物制药产品提供了显著降低成本和创造几乎无限供应的无病原体重组蛋白源材料的潜力。然而，与任何重组蛋白生产系统一样，必须严格建立每个生物工程植物系统的工艺一致性，并确定过程控制，以确保始终如一地生产安全有效的药物。本研究的长期目标是建立一个良好的特征化的生产平台，满足当前良好生产规范（cGMP）的要求，可用于从生物工程马铃薯植物的叶子中低成本生产高质量、无病原体的重组蛋白。该提案描述了基于申请人的创新方法的研究，该方法用于在明确定义的环境条件下使用密切监测的模块化生长室来生长和收获马铃薯植物叶子，该生长室可扩展以满足许多已建立和新兴生物制药产品的全球医疗需求。在拟议研究的第一阶段，目标是表征模型生物工程马铃薯植物的生长，并监测重组蛋白表达的可测量变化，包括研究规模生产活动过程中的数量和质量（蛋白质结构和功能）。本研究的结果将确定并建立过程中监测参数，以评价收获的散装产品的总体生产一致性。在此阶段预期成功的可能性很高，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物的稳健方法。此外，M博士。Bluebird Biosciences，Inc.的Griffith，他拥有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，以记录生产活动期间模型蛋白质的结构和功能。根据这些信息，将提交II期研究提案，以扩大生产活动，以获得足够的生物质用于重组蛋白纯化和详细的生化表征。

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.