Automated Production of Plant-Based Vaccines and Pharmaceuticals

Wirz, Holger; Sauer-Budge, Alexis F.; Briggs, John D.; Sharpe, Aaron; Shu, Sudong; Sharon, André

doi:10.1177/2211068212460037

Cited by 57 publications

(37 citation statements)

References 11 publications

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“…The temperature and humidity in the growth room ranged from 23–26°C and 20–60%, respectively. This hydroponic plant growth system is a small-scale arrangement that can be scaled to cGMP pilot scale production [28]. For a comparison of germination and biomass accumulation rates, CTB-FIX plants were grown alongside the commercial cultivar Simpson Elite.…”

Section: Methodsmentioning

confidence: 99%

Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B

et al. 2015

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Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (~1mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ~2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP+ regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ~870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft2 per annum yielding 24,000–36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs.

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Section: Methodsmentioning

confidence: 99%

Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B

et al. 2015

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“…Other groups have intensified their efforts to develop a new regulatory pathway for whole plants (Figure 2) resulting in updated guidelines [49]. There have been impressive efforts to incorporate the latest regulatory innovations in plant-based manufacturing processes, including quality by design through the use of statistical experimental models to optimize each production process [28,29 ], process analytical technologies to improve product quality and consistency [22], automated production platforms to increase process robustness and scalability [50] and single-use technologies to reduce the risk of contamination and product carry-over, including single use bioreactors [16 , 51,52], novel filter materials [42] and chromatography media [40].…”

Section: Regulatory Considerationsmentioning

confidence: 99%

High-value products from plants: the challenges of process optimization

Fischer¹,

Vasil'ev²,

Twyman³

et al. 2015

Current Opinion in Biotechnology

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“…This facility handles all aspects from seeding to harvest in a nearly lights-off manner. 35 Concerns of containment and compatibility of using plants for cGMP process has been advanced by tightly controlled and contained indoor environments. 32 In addition to the Fraunhofer facility, the large-scale plant expressed protein manufacturers of Kentucky BioProcessing (Owensboro, KY), Medicago Inc. (North Carolina) and Caliper Biotherapeutics (College Station, Texas) all have manufacturing facilities with various levels of robotic and flexible use facilities.…”

Section: Discussionmentioning

confidence: 99%