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.

中文翻译：

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为植物分子农业生产的重组蛋白提供无缝的产品和工艺开发工作流程


植物分子农业 (PMF) 已被推广为一种快速、高效且经济高效的细菌和动物细胞替代品，用于生产生物制药蛋白。许多植物品种已经过测试，可生产多种候选药物。然而，PMF普遍缺乏系统、精简、无缝的工作流程来持续填充产品管道。因此，目前在常规、通量和横向集成（候选产品快速转化为临床前和临床开发）方面无法与现有平台竞争。个人管理决策、有限的资金和缺乏合格的生产能力可能会阻碍此类项目的执行，但我们也缺乏合适的样品处理和数据管理技术。这篇观点文章将强调 PMF 当前的瓶颈，并提供潜在的解决方案，将 PMF 与现有技术相结合，构建未来的产品开发、测试、制造和临床转化的集成设施。已确定并依次讨论了十大瓶颈：自动克隆和简化的转化选项、细菌培养的可重复性、生物反应器与自动细胞处理的集成、快速中型候选物和产品制造的选项、与（群体特定或个性化）的互连）临床试验、（后）渗透条件的多样性、下游加工平台的开发、连续工艺操作、制造条件符合生物安全法规、级联生物质的扩展要求。