1. Methods
Safety
• Special care must be taken in the production of stem cells and neural cells because
they will be used in humans
• A clean room will be used to handle any materials put into or taken out of the process
• Final product must be free of viruses and bacteria; a filter will be used to remove these
and they will be inactivated using sodium hydroxide
• The waste from the process has some hazards associated with it
• All waste must be inactivated before being sent to the sewer
• Sodium hydroxide is used to inactivate any living organisms in the waste
stream
• A containment area will be used to treat and store waste before dumping to
sewer
• Personal protective equipment should be used
• Impervious gloves
• Safety glasses with side shields
• Lightweight protective clothing
Economics
Equipment costs were made using industry quotes and estimations
Working capital of 3% of total depreciable capital was assumed
Straight-line depreciation over ten-year period assumed
Total Depreciable Capital: $87 Million
Depreciation was 26% of total yearly fixed costs
Total Capital Investment: $90 Million
Net Present Worth: $242 Million
Feature
• Microcarriers are optimized for MSC applications
• Using different stages can use time adequately for cell expansion
• Adding minus vitamin A will increase the rate of stem cell transferring to neural cell
• Stem cell expansion bioreactor will guarantee the yield of the stem cell instead of
differentiation ahead of time
• The bioprocess can be scaled up as increasing quantity demanded
Discussion
Cell Therapy for Spinal Cord Injuries:
Commercial Manufacturing Facility
Hui Dong and Adeline Ford
Abstract
The design of a manufacturing facility to produce neural stem cells from adult stem cells
• Overall fixed capital: $83.5 Million
• Cash Flow Payout Period: 2.4 years
• Total Equipment Cost: $18 Million
• Lang Factor: 4
• Total Installed Costs: $72.6 Million
• Plant Capacity: 13,440 Treatments/year
• IRR: 50%
• Breakeven Selling Price: $2,856/treatment
• Actual Selling Price: $8,380/treatment
• Return on Investment: 31%
• Stage feeding cells and expansion
• Stem cells bioreactor aimed at expansion
• Own designed differentiation Bioreactor
1) "Spinal Cord Injury Fact Sheet." California's Stem Cell Agency. N.p., 26 Oct. 2009. Web. 01 Feb. 2016. . 2) "Spinal Cord Injuries: How Could Stem Cells Help?" EuroStemCell. N.p., 2 Apr. 2015. Web. 05 Feb. 2016. . 3) Peters, Max S., Klaus D. Timmerhaus, and Ronald E.
West. Plant Design and Economics for Chemical Engineers. New York: McGraw-Hill, 2003. Print. 4) "Payback Period Formula - AccountingTools." Payback Period Formula - AccountingTools. N.p., n.d. Web. 02 Oct. 2015. . 5) Seider, Warren D., J. D. Seader, Daniel R. Lewin, and
Warren D. Seider. Product and Process Design Principles: Synthesis, Analysis, and Evaluation. New York: Wiley, 2004. Print. 6) Shukla, Abhinav A., Mark Raymond. Etzel, and Shishir Gadam. Process Scale Bioseparations for the Biopharmaceutical Industry. Boca Raton:
CRC/Taylor & Francis, 2007. Print. 7) "Large-scale Expansion of Stem Cells for Therapy and Screening. Winter 13." Drug Discovery World. N.p., n.d. Web. 14 Feb. 2016. . 8) "Biotechnology JournalVolume 6, Issue 11, Article First Published Online: 1 JUL 2011." Stem Cell Culture
Engineering – Process Scale up and beyond. N.p., n.d. Web. 14 Feb. 2016. . 9) Zhu, Beili, and Shashi K. Murthy. "Stem Cell Separation Technologies." Current Opinion in Chemical Engineering. U.S. National Library of Medicine, 1 Feb. 2013. Web. 14 Feb. 2016. . 10) Duchez,
Pascale, Bernard Dazey, Luc Douay, Gerard Vezon, and Zoran Ivanovic. "An Efficient Large-Scale Thawing Procedure for Cord Blood Cells Destined for Selection and Ex Vivo Expansion of CD34 + Cells." Journal of Hematotherapy & Stem Cell Research 12.5 (2003): 587-89.
Web. 14 Feb. 2016. 11) Duchez, Pascale, Bernard Dazey, Luc Douay, Gerard Vezon, and Zoran Ivanovic. "An Efficient Large-Scale Thawing Procedure for Cord Blood Cells Destined for Selection and Ex Vivo Expansion of CD34 + Cells." Journal of Hematotherapy & Stem Cell
Research 12.5 (2003): 587-89. Web. 14 Feb. 2016. 12) Note, Application. Large-scale Production of Human Mesenchymal Stem Cells in BioBLU ® 5c Single-use Vessels (n.d.): n. pag. Web. 14 Feb. 2016. 19 13) N.p., n.d. Web. 14 Feb. 2016. .
Conclusion and Recommendations
A neural cell production plant from adult stem cells is an economically beneficial project.
A favorable return on investment of 31% and cash flow payout period of 2.4 years.
Recommendations
• Increase the capacity of the plant
• Allow for treating more people and expansion to the European market
• Distribution of fixed costs- economies of scale
• Medium is the most expensive fixed cost- research a less expensive medium
• Research if cells could be grown onsite for reactor inoculum to decrease costs
• Determine the exact number of treatments needed per year
Figure 1: Process Flow Diagram
Acknowledgements
We would like to thank Michigan State University for providing the education and training
necessary for this design to be completed. Dr. Hawley also provided support and
guidance for this project. We would also like to thank AICHE for providing this design
problem. Finally, we would like to thank all of the MSU Chemical Engineering Faculty for
teaching us all of the skills that we need to be professional chemical engineers.
There are currently over 250,000 people in the US with spinal cord injuries and every
year about 12,000 more people are injured in the US.1
Spinal cord injuries can be treated with stem cell treatments.
Up to 20 Million cells are needed for each treatment.2
Adult stem cells are attached cell lines; they are not grown in suspension reactors
Stem cells differentiated into neural cells
This facility:
• Takes adult stem cells from bone marrow
• Use premade medium to expand stem cells
• Cells differentiated to neural cells using premade supplement
• Neural cells processed and separated and viruses removed and inactivated
Introduction
Second setoflarge bioreactor
10 m edium bioreactors
10 m edium bioreactors
10 m edium bioreactors
1 large bioreactor
10 m edium bioreactorsSecond setofm edium bioreactors
0 sm allbioreactors Fourth group 100 sm allbioreactors
10 m edium bioreactors
Firstsetoflarge bioreactor
Third group 100 sm allbioreactors
Shift1(200 hrs)
Firstgroup 100 sm allbioreactors Fifth group 100 sm allbioreactors
10 m edium bioreactors
Sixth group 100 sm allbioreactors
Firstsetofm edium bioreactors
Blue m eans20 hrscleaning
10 m edium bioreactors 10 m edium bioreactors
1 large bioreactor 1 large bioreactor
Shift3(1000hrs+ 100hrstransfertim e)
100 sm allbioreactors 100 sm allbioreactors 100 sm allbioreactors 100 sm allbioreactors 100 sm allbioreactors 100 sm allbioreactors 100 sm allbioreactors
Shift2(400hrs+ 20hrstransfertim e)
Second group 100 sm allbioreactors
10 m edium bioreactors 10 m edium bioreactors
10 m edium bioreactors
10 m edium bioreactors
Figure 2: Process Media
Figure 3: Expansion Schedule
Figure 5: Differentiation Bioreactor
Figure 4: Expansion Bioreactors