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. ? ?
