Team
Eporis consists of four Chemical
Engineering seniors at Calvin College
(Figure 1). Core strengths include
biochemistry research experience,
pharmaceutical process development, and
financial management. They are
coordinating their efforts to reduce the
high costs associated with the
biotechnology industry.
Project Background
Figure 1. Eporis: Zion Lee, Nick Giles, Stephen
Tubergen, Abby Leistra, left to right.
Erythropoietin (EPO) is a glycoprotein hormone that promotes red blood cell production (Figure 2). It is
naturally made by the human kidneys; however, it is often prescribed to treat anemia in patients
undergoing medical treatments, including dialysis, chemotherapy, and HIV therapy. It represents a $4
billion annual market in the US.
EPO is a biologic drug, meaning it is produced in a living cell system. Currently, commercial varieties are
produced from mammalian cells. These systems are slow-growing and require many purification steps.
We propose production of EPO in the faster growing Pichia Pastoris (P. Pastoris) yeast cell line.
Furthermore, this method reduces the number of purification steps required.
Design
Genetic Modification
Eporis plans to use genetically engineered P. Pastoris strains
to allow the mammalian protein, EPO, to be produced by
simple yeast. Genetic changes to the yeast strain will enable
it to produce bioactive EPO and produce it at greater yields.
PEGylation
Further product modification is necessary for P. Pastorisproduced EPO to be as effective as mammalian cellproduced EPO. A polyethylene glycol (PEG) group will be
added to the protein to increase its molecular weight and
negative charge, increasing bioactivity to a level equivalent
to current commercial products.
Figure 2. Erythropoietin structure.
(glycam.org)
Fermentation
Genetically engineered P. Pastoris will be grown in a
type of reaction vessel known as a fermenter (Figure
3). In order to maximize EPO production, the
fermentation process will be semi-batch, i.e. a few
materials will be added with time over the course of
the fermentation while most will be added in bulk at
the start of fermentation. Feedstock composition and
flow rate, oxygenation, and agitation will all affect cell
growth and EPO production.
Separation
The separation processes associated with EPO
produced from P. Pastoris are more effective than
with those associated with EPO produced from CHO
cells. Because P. Pastoris secretes few native
proteins, our process will produce a much cleaner
bioreactor effluent, resulting in higher purity with
fewer chromatography steps. Furthermore, virus
transmission is impossible with yeast, so viral
inactivation stages can be neglected with this
Figure 3. Stainless steel fermenter. (en.wikipedia.org) process.
Business Model
The expiration of American EPO patents is a great opportunity for entry of new biopharmaceutical
companies. When several other companies wish to join this market for biosimilar EPO (based on similar
historical instances), there will be demand for Eporis’ drug substance. On the off chance that other
companies do not enter the market, Eporis has the option to contract out drug product manufacturing
and enter the market until there is competition. With the current markup of on-patent drugs, Eporis will
command a significant margin from its manufacturing cost leadership. With the expected approval of
the FDA, Eporis can also consider entering (or supplying) other global markets.
Figure 4. Eporis considers all aspects of the biopharmaceutical market landscape. This
includes drug production, distribution, and administration. (sparkblog.emc.com)