title: Bulk production of the antiviral lectin griffithsin.
abstract: Application of plant-based protein expression systems for bulk production of recombinant protein pharmaceuticals is building momentum. There are considerable regulatory challenges to consider in commercialization of plant-made pharmaceuticals (PMPs), some of which are inherent to plant-production systems and others that are common with other production systems, but are new to PMPs because of the youth of the industry. In this review, we discuss our recent and ongoing experience with bulk production of the HIV microbicide candidate, griffithsin (GRFT), utilizing plant-based transient protein expression, with specific focus on areas relevant to commercial manufacturing of bulk GRFT active pharmaceutical ingredient (API). Analytical programs have been developed for the qualification and monitoring of both the expression vector system and the API detailing our experience and plans for each. Monitoring postpurification protein modifications are discussed in relation to stability and safety programs. Expression, processing and analytics programs are associated with increased manufacturing costs in current good manufacturing practice (cGMP) production because of the required qualification testing. The impact of these costs on the overall cost of goods is particularly relevant to GRFT manufacturing because GRFT, as an HIV microbicide, is most needed in populations at high risk for HIV exposure in resource-poor countries. Consequently, GRFT for microbicide applications is a very cost-sensitive recombinant PMP. We have therefore emphasized maintaining a low cost of goods. We provide a review of the literature on the economics of PMPs with various expression systems and how they may impact production costs and complexity.
authors.affiliation: Owensboro Cancer Research Program, Owensboro, KY, USA.|Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Fuqua
authors.affiliation: Owensboro Cancer Research Program, Owensboro, KY, USA.|Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Krystal
authors.initials: K
authors.lastname: Hamorsky
authors.affiliation: Intrucept Biomedicine, LLC, Owensboro, KY, USA.
authors.forename: Guruatma
authors.initials: G
authors.lastname: Khalsa
authors.affiliation: Owensboro Cancer Research Program, Owensboro, KY, USA.|Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matoba
authors.affiliation: Owensboro Cancer Research Program, Owensboro, KY, USA.|Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Palmer
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D002298:Cardenolides / Q000378:metabolism*; D037102:Lectins / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D010957:Plasmids / Q000378:metabolism; D014771:Virion / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D002298:Cardenolides; D037102:Lectins; C529099:griffithin
keywords: HIV; griffithsin; microbicide; protein oxidation; tobacco mosaic virus; virion