Towards a seamless product and process development workflow for recombinant proteins produced by plant molecular farming.

Plant molecular farming (PMF) has been promoted as a fast, efficient and cost-effective alternative to bacteria and animal cells for the production of biopharmaceutical proteins. Numerous plant species have been tested to produce a wide range of drug candidates. However, PMF generally lacks a systematic, streamlined and seamless workflow to continuously fill the product pipeline. Therefore, it is currently unable to compete with established platforms in terms of routine, throughput and horizontal integration (the rapid translation of product candidates to preclinical and clinical development). Individual management decisions, limited funding and a lack of qualified production capacity can hinder the execution of such projects, but we also lack suitable technologies for sample handling and data management. This perspectives article will highlight current bottlenecks in PMF and offer potential solutions that combine PMF with existing technologies to build an integrated facility of the future for product development, testing, manufacturing and clinical translation. Ten major bottlenecks have been identified and are discussed in turn: automated cloning and simplified transformation options, reproducibility of bacterial cultivation, bioreactor integration with automated cell handling, options for rapid mid-scale candidate and product manufacturing, interconnection with (group-specific or personalized) clinical trials, diversity of (post-)infiltration conditions, development of downstream processing platforms, continuous process operation, compliance of manufacturing conditions with biosafety regulations, scaling requirements for cascading biomass.