FEL-2 Feasibility Study: GreenGene Process is financially robust based on Penicillin G study
1. FEL-2 Feasibility Study: GreenGene
SMITH GROUP – Hayoung Lee, Soo Lee, Iyore Olaye, Sang Yoo
School of Chemical and Biomolecular Engineering
Cornell University
Ithaca, NY 14853
May 8, 2016
2. Table of Contents
I. Project Statement
II. Market Analysis
III. Process Units
IV. Plant Location and Plant Layout
V. Constructability
VI. Economic Analysis
VII. Recommendation for FEL-3
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SMITH
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GreenGene May 9, 2016
3. Project Statement
q Client: NanoBio Pharmaceuticals
• New product : GreenGene (anti-hypertensive drug)
• Modeled using Penicillin G production process
q Objective
• Capture 20% of the North American market after 5 years
• Produce 120% of the estimated year five demand
• Assumed dosage: 100mg/day
q Determine
• Capital and operating costs for the facility
• Ex-plant price of GreenGene proxy
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GreenGene May 9, 2016
4. GreenGene Feasibility Study
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GreenGene
Process is financially robust based on Penicillin G study
Proceed to FEL-3 Stage
May 9, 2016
Location?
Fairfax, Iowa
Economic Analysis?
Price per dose at 18% DCFROR: $0.008/dose
Based on Penicillin G production process
Average Competitive price per dose of hypertension API: $0.03/dose
Total Project Cost: $110 MM
Operating Cost: $21 MM
Environmental Concerns?
No significant environmental or safety concerns
6. Market Analysis
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GreenGene May 9, 2016
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
5.00
0 1 2 3 4 5 6 7 8 9 10
AmountofAnti-hypertensiveDrug(Tg)
Years of Production 2019
q Target Market :
North Americans with Hypertension
q 100 mg dose per day
q Economic Goals for GreenGene:
• Capture 20 % of total market
• Supply 120% of demand by year 5
Supply estimate served as a basis for equipment sizing and
economic analysis throughout FEL-2 study
Annual demand
Annual supply
High Blood Pressure Facts." Centers for Disease Control and
Prevention. Centers for Disease Control and Prevention, 19 Feb.
2015. Web. 09 May 2016.
11. Fermentation
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GreenGene May 9, 2016
See PFD: Process Sheet 2
Objective: Purify air to meet pharmaceutical standards / Achieve
desired concentration of titer through controlled reaction kinetics
13. Reaction Basics
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GreenGene
Main Reaction :
Cell + Glucose + O2 + PAA + (NH4)2SO4
à More Cells + Penicillin G + CO2 + H2O + Heat
Penicillin G
Penillic Acid
Penicilloic Acid
Degradation of Penicillin G (Side Reactions) :
May 9, 2016
Birol, Gülnur, Cenk Ündey, and Ali Çinar. "A Modular Simulation
Package for Fed-batch Fermentation: Penicillin Production." Computers
& Chemical Engineering 26.11 (2002): 1553-565. Web.
14. 0
50
100
150
200
250
300
350
400
450
500
0 50 100 150 200
Concentration(g/L)
Time (hr)
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GreenGene
[Glucose]
[Cell]
[Penicillin G]
Chemical Reaction Kinetics
• Based on Bajpai & Reuss
kinetic model
• [Cell]max = [Glucose]min
• [Cell]min = [Glucose]max
• Stress fermenter 4
May 9, 2016
After 200 total hours, 50 g/L
of [Penicillin G] is achieved
15. 15
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GreenGene
Chemical Reaction Kinetics-Penicillin G
• 18th Hour [Substrate] = 0
growth is constant at a
maximum
• Batch Mode = 7 hours
• Stress = 50 hours
0
10
20
30
40
50
60
0 20 40 60 80 100 120 140
Concentration(g/L)
Time (hr)
Batch
Stress
May 9, 2016
What about the production goal?
16. Penicillin G Degradation Rate
• Penicillin degradation is a first
order reaction
• After 50 hours of stressing,
40g/L remains
• After 90 hours of stressing,
40g/L remains due to higher
degradation rate
A. Kheirolomoom et al., The combined effects of pH and
temperature on penicillin G decomposition and its stability
modeling Process Biochemistry.. 35: 205-211, 1999
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GreenGene
Shorter time still yields the same amount of Penicillin G
v
ç pH 6.8
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!
!!
= −!"!
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!
May 9, 2016
17. 0
10
20
30
40
50
60
0 2 4 6 8 10 12 14
PenicillinG(g/L)
pH
Sensitivity Analysis on pH
• [Penicillin G]max at pH 7
• Optimal operating range: 6.5-7.5
• pH 7 ± 2 yields only 80% [Penicillin G]max
• VERY SENSITIVE!!!!
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GreenGene
Optimal pH during stressing is 6.5 – 7.5
Variation in pH has a significant impact
May 9, 2016
A. Kheirolomoom et al., The combined effects of pH and
temperature on penicillin G decomposition and its stability
modeling Process Biochemistry.. 35: 205-211, 1999
18. Example of Process Control
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GreenGene
q Process Control Objective
• Provide oxygen to keep cells alive
• Maintain constant pH at 6.5
q Process Control Strategy
• Monitor the concentration of air and
pH level
• Implement a feed forward control loop
based on the kinetic model
May 9, 2016
29. Water and Biowaste Treatment
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GreenGene May 9, 2016
See PFD: Utilities Sheet 1,2
Objective: Purify water to meet pharmaceutical standards / Treat
any waste produced by the plant to meet the EPA regulations
32. Environmental and Health Issues
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GreenGene
q Environmental Design Considerations
q Health Issues
May 9, 2016
Boiler
• Burn off-gas from fermenters and biodigestors
• Prevent toxic gas release to atmosphere
Biodigestors • Treat biowaste properly
EPA regulations
• Clean Air Act
• Waste effluent limitation
Protection of Plant
Personnel
• Personal protective equipment: eyewear, gloves, etc.
• Hazard communication trainings
Accident Prevention/
Emergency Response
• Toxicity detectors to indicate exposure
• In case of leakage
- Have the necessary clean up materials ready
- Have trained personnel to clean up the area
"US Environmental Protection Agency." US Environmental
Protection Agency. Web. 09 May 2016.
33. Safety Issues
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GreenGene
q General Considerations
• Fire prevention
• Fire suppression
• Dust explosion prevention
q Greatest risk: Tornado
• Build underground shelter
• Emergency response plan
May 9, 2016
No significant safety concerns
A. Kheirolomoom et al., The combined effects of pH and
temperature on penicillin G decomposition and its stability
modeling Process Biochemistry.. 35: 205-211, 1999
35. 35
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GreenGene May 9, 2016
Plant Location Considerations
• Proximity to major raw materials
– Corn steep liquor
• Ease of transportation for
materials/ equipment/ product
– Railroad, highway
• Weather conditions
– Tornado
Location: Fairfax, Iowa
42. Labor Requirements
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GreenGene
5 8 12
25
40
98
165
180
155
55
Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10
#ofLarborers
Quarter of Project TImeline
May 9, 2016
Maximum number of laborers = 200
Will not impact the surrounding city; labor need can be fulfilled
43. Startup and Shut Down Procedure
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GreenGene April 27, 2016
Startup
1. Activate electrical system
2. Activate fire and water systems
3. Activate natural gas/
instrument
4. Fill Cooling-water system and
circulate
5. Activate air and steam systems
6. Turn on boiler
7. Start air compressors
8. Start feed to the biodigestor
9. Sterilize media using steam
10. Start up one fermenter train at
a time
Shut Down
1. Remove hazardous process
materials
2. Reroute streams to
designated area
3. Turn heat and coolant off
4. De-pressure the systems
5. Isolate the systems from other
processes
6. If shut down prolongs, protect
the equipmentfrom
deteriorating
No significant deviation from the standard procedure
45. ICARUS Summary Costs
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GreenGene
Item Cost (MM$)
Equipment 9.0
Equipment Setting 0.34
Piping 5.4
Civil
(Building & Construction)
16
Steel 0.54
Instrumentation
(Model Base Controls)
7.0
Electrical 3.8
Insulation 0.44
Paint 0.45
Other 38
G and A Overheads 3.0
Owner’s Costs 6.6
Total Project Cost: $110 MM with 25 % contingency
May 9, 2016
46. Economic Analysis Breakdown
Item Cost ($MM)
Annual Amount of Product Sold 10,500 (MM of Doses)
Total Sales Revenue
(at .008 cent/dose)
84
Raw Material Cost 4.0
Variable Costs 4.0
Fixed Costs 6.5
Gross Margin 74
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GreenGene
Operating ramp-up:
Initial Start Up: 50 % Capacity
Ramp up linearly to 100 % in year 5
Determining product price:
DCFROR: 18% (NPV: 0) in year 10 at 100% capacity
May 9, 2016
48. Sensitivity Analysis - Controllable
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GreenGene
0 0.002 0.004 0.006 0.008 0.01 0.012 0.014 0.016
Years until Full Capacity
Total Invested Capital
No. of Batches
Labor Cost
Cost per Dose ($)
Attention should be given to the number of failed batches
to ensure product price consistency
2 years
7 years
± 30%
- 5%
± 30%
May 9, 2016
VariableFactors
49. Sensitivity Analysis - Uncontrollable
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GreenGene
0.0064 0.0069 0.0074 0.0079 0.0084 0.0089 0.0094
± 30%
± 10%
Attention should be given to the amount sold to ensure
product price consistency.
Cost per Dose ($)
Amount Sold
Fixed Cost
Raw Material Cost
± 30%
May 9, 2016
VariableFactors
50. Economic Analysis
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GreenGene May 9, 2016
Total Project Cost: $110 MM
• Working Capital: $21.0 MMCost Summary
Price/dose at 18% DCFROR: $0.008
• Based on Penicillin G production
process
Pricing Strategy
No significant deviation
Insensitive overall, thus financially
robust
Sensitivity Analysis
52. Recommendation for FEL-3
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SMITH
Group
GreenGene
• Kinetic modeling based on GreenGene
• Revisit optimization and control strategy for solvent
recovery systems
• Products and in-process quality control sampling
May 9, 2016
Revalidate and modify the process based on GreenGene
