Product safety aspects of plant molecular farming

Abstract

Plant molecular farming (PMF) has been promoted since the 1990s as a rapid, cost-effective and (most of all) safe alternative to the cultivation of bacteria or animal cells for the production of biopharmaceutical proteins. Numerous plant species have been investigated for the production of a broad range of protein-based drug candidates. The inherent safety of these products is frequently highlighted as an advantage of PMF because plant viruses do not replicate in humans and vice versa. However, a more nuanced analysis of this principle is required when considering other pathogens because toxic compounds pose a risk even in the absence of replication. Similarly, it is necessary to assess the risks associated with the host system (e.g., the presence of toxic secondary metabolites) and the production approach (e.g., transient expression based on bacterial infiltration substantially increases the endotoxin load). This review considers the most relevant host systems in terms of their toxicity profile, including the presence of secondary metabolites, and the risks arising from the persistence of these substances after downstream processing and product purification. Similarly, we discuss a range of plant pathogens and disease vectors that can influence product safety, for example, due to the release of toxins. The ability of downstream unit operations to remove contaminants and process-related toxic impurities such as endotoxins is also addressed. This overview of plant-based production, focusing on product safety aspects, provides recommendations that will allow stakeholders to choose the most appropriate strategies for process development.

Production of monoclonal antibodies against botulinum neurotoxin in Nicotiana benthamiana

“… 58 However, unlike cell cultures, exposing a product to non-sterile and non-aseptic conditions may result in regulatory scrutiny. 59 , 60 In this work, the production of antibody-based BoNT antitoxins such as mAbs 1B18, C25, and M2 in N. benthamiana was investigated.…”

Membrane-based inverse-transition purification facilitates a rapid isolation of various spider-silk elastin-like polypeptide fusion proteins from extracts of transgenic tobacco

“…Plants can have several advantages for the production of biopharmaceutical proteins such as low upstream production costs of ~ 50 € kg −1 wet biomass due to simple cultivation (Ridgley et al 2023 ) and an inherent safety because they do not support the replication of human pathogens (Schillberg et al 2019 ; Donini and Marusic 2019 ; Moustafa et al 2016 ; Tschofen et al 2016 ; Buyel 2023 ). However, the recovery of recombinant proteins from plant extracts can be challenging due to large quantities of particles and host cell proteins that are typically released during biomass homogenization (Wilken and Nikolov 2012 ; Buyel 2015 ).…”