| Commercialization of any biotechnology product or pharmaceutical is a complex process with many technical, economic and industrial aspects that can negatively impact feasibility. Successful manufacturing is not in itself sufficient for successful commercialization---facets of regulatory approval, ethical considerations, public acceptance and competitive market forces may each inhibit the introduction and use of new technologies. Plant-made vaccines (PMVs) have attracted much interest from academic researchers and the general public for more than 15 years, but have not been successfully commercialized for human use---the focus of this dissertation. A situational analysis was completed to review the strengths, weaknesses, opportunities and threats to further development of this technology. A method for downstream processing was established for batch production of stable and consistent materials from perishable plant sources. The production, processing, extraction and quantitation for a leading PMV candidate---a norovirus vaccine expressed in transgenic tomato---was optimized for potential clinical use and as a model for development of other PMV candidates. Justification and suggested dose of Quillaja saponaria as a potential oral adjuvant in humans---a critical priority for PMV development---was provided, and its preclinical use with PMVs was reviewed. A comprehensive assessment of the environmental and health risks associated with PMV manufacturing was assembled with analysis on how these risks must be managed as a combination of agricultural and pharmaceutical regulations. The use of PMVs was examined in relation to ethical issues in three domains---as genetically modified plants, as clinical research materials, and as agents of global health. The consideration of commercial feasibility was recommended as a practical and ethical requirement prior to human clinical testing with new agents, and PMV technology was used as a model for this proposal. The potential for social acceptance of a PMV was evaluated for the first time by means of a public opinion survey of 706 respondents, and indicated good support for a potential oral vaccine produced in a transgenic plant, and for biotechnology in general. Commercial feasibility of the PMV technology platform was explored by modeling three potential PMVs with detailed evaluation of the technical, economic and industrial aspects for each product. |
