Process Development Strategies in Plant Molecular Farming

Protein-based biopharmaceuticals are often produced in mammalian cell cultures, which are more expensive than microbial systems but capable of authentic post-translational modifications. The costs are lower if plants are used as an alternative platform to produce complex proteins such as monoclonal antibodies, vaccines and enzymes. This review highlights recent advances that have been achieved in plant-based biopharmaceutical production platforms in terms of expression strategies, product yields and process development. The first generation of plant-derived pharmaceuticals now entering the market is also discussed. Finally, the review considers the downstream processing of plant-derived pharmaceuticals which can account for up to 80% of the production costs. In this context, recent improvements in clarification and integrated process methods will have a strong impact on the economic feasibility of production, especially if supported by and combined with process analytical technology as part of the quality-by-design initiative. Keywords: Plant-made pharmaceuticals, recombinant protein expression, process scale-up and automation, clarification procedures, downstream processing, integrated purification strategies.