BioMed Research International / 2014 / Article / Tab 1

Research Article

Manufacturing Economics of Plant-Made Biologics: Case Studies in Therapeutic and Industrial Enzymes

Table 1

Recombinant butyrylcholinesterase (rBuChE) design premises and key assumptions.

ParameterValue

General assumptions for the facility
rBuChE production level 25 kg rBuChE/year (bulk)
rBuChE doses per year62,500 doses/year at 400 mg/dose
Downstream Recovery/purification yield20%
Annual operating days330 days
rBuChE production in plants following infiltration/incubation125 kg rBuChE/year
Batch cycle time (time between start of new infiltration batches)7 days
Batches per year47
Base case rBuChE expression level500 mg/kg FW at ~7 days after infiltration
Facility lifetime15 years
DepreciationStraight line over 10 years, 5% direct fixed capital salvage
Working capital30 days of labor, materials, utilities, waste treatment
Lab/QC/QA costs2% of total labor costs for plant growth and agroinfiltration sections, 15% of total labor costs for recovery and purification section
Start-up/validation costs5% direct fixed capital

Assumptions for indoor plant growth section
Mass per plant at 5 weeks0.02 kg FW/plant
Tray size4 ft × 4 ft
Number of plants per tray256
Tobacco seed cost$0.001/seed
Age at infiltration4 weeks
Total number of plant batches in inventory5 batches (just seeded, 1 wk old, 2 wk old, 3 wk old, 4 wk old—ready to infiltrate, 5 wk old—infiltrated, incubated and ready to harvest)
Total number of plants in inventory~1.3 million
Total plant growth area83,320 ft2 total, or 10 levels with 8,332 ft2 footprint
LED fixture costs$40/ft2 plant growth area (including capital cost factors for plant growth area as shown in Table 2)
LED energy costs 20 W/ft2

Assumptions for Agrobacterium production, vacuum infiltration, and plant incubation section
Agro “loading”—mass of recombinant Agrobacterium to mass of plant tissue0.00001 kg dry weight (dw) bacteria/kg FW plant biomass
Agrobacterium biomass density at 12 hours of culture2.6 g dw/L = 0.0026 kg dw/L
Inoculum density used in seed train1% V/V
Dilution factor between agroinfiltration solution and agrobacterial production fermentor78
Percent weight change in plant tissue following vacuum agroinfiltration30%
Trays processed per vacuum chamber (30 ft) per day336 trays/chamber/day
“Excess” Agrobacterium solution used87% of total infiltration solution
Incubation time for infiltrated plants~7 days

Assumptions for the rBuChE recovery and purification section
Overall yield in downstream processes20%
Harvesting rate3 trays/minute
IEX chromatography
 Binding capacity20 mg/mL
 Resin cost$1,839/L
 Number of reuse cycles100
Affinity chromatography
 Binding capacity3 mg/mL
 Resin cost$10,000/L
 Number of reuse cycles30

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