Large scale production of Recombinant Human Erythropoietin (rhEPO) using Chinese Hamster Ovary (CHO) Cell Line Md. Shawkat Hossain1, Rubayat Jamal1, Md. Tariq Hasan1, M.A.G. Rabbani1, Abdullah Al Maruf1, Dr. Md. Iqbal Hassan Khan1 1
Research & Development, Biotechnology Derived Product Facility, Incepta Pharmaceuticals Ltd, Dewan Idrish Road, Zirabo, Savar, Dhaka, Bangladesh * Correspondence to:
[email protected] Abstract
Recombinant EPO Production RecombinantAEPO p pProduction r o a c h Approach
Erythropoietin (EPO) stimulates the proliferation and differentiation of erythroid cells, leading to an increase in the number of reticulocytes in the blood, which consequently increases the blood’s haemoglobin concentration. This hormone is mainly produced in the kidney in human adults, and anaemia associated with renal failure often results from decreased levels of Erythropoietin. In this poster we have demonstrated the generalized commercial and scientific idea behind the recombinant human Erythropoietin Beginning
Wo r l d M a r k e t o f r h E P O Top 10 Biosimilars world wide in respect of earning revenue
In the late 1970s, Dr. Goldwasser, working at the University of Chicago, isolated and purified erythropoietin . He then shared his findings with a young biotechnology company, which figured out how to produce larger amounts of the protein using genetic engineering. That company, Amgen, became the world’s biggest biotechnology company on the basis of EPO. Sales of erythropoietin under names like Epogen, Procrit and Aranesp amounted to billions of dollars a year for Amgen, as well as Johnson & Johnson and Roche 1
EPO Production Process
Mechanism of Action
Comparison between Total Market Revenue and the Revenue Earned by Incepta in case of Insulin and Erythropoietin (per month) Culture Flask Seed Culture
Media Recombinant Human Erythropoietin
Roller Bottle Incubator
Process flow for rhEPO production
Recombinant Human Insulin
3
25
2.5
AKTA Pilot
2.58
Recombinant Human 20 Insulin
Revenue in Crore
Revenue in Crore
Recombinant Human 2 Erythropoietin
0.71
1.5 1 0.5
Recombinant human erythropoietin
Selection of Animal Model
3
Total market revene (crore)
Revenue earned by Incepta (crore)
15
10
5
0
Total market revene (crore)
24.7
0
Revenue earned by Incepta (crore)
Major Equipments
Expression in Animal Cells • Naturally glycosylated produced in:
AKTA Pilot
Bioreactor
DNA Sequencer
FACS
Roller Bottle Incubator
– – – – – – –
Biopharmaceuticals company
Product name
Revenue (crore per month)
Total market share %
Market position
Roche
Recormon & Mircera
2
66.66
1st
Incepta
Epoetin
0.71
23.67
2nd
Beacon
Eposis
0.29
9.67
3rd
proteins
CHO - Chinese Hamster Ovary BHK - Baby Hamster Kidney HEK -Human Embryonic Kidney BMS - Bristol Myers Squibb Mouse Myeloma (NS0) Cells Hybridoma cells Murine myeloma
• The most widely used mammalian expression system is the gene amplification procedure offered by CHO cells
Market share of Recombinant Human Erythropoietin in Bangladesh Fig.: Chinese hamster
10%
Roche 24%
Incepta 66%
Beacon Fig: Chinese hamster ovary (CHO) cells in cell culture flask
Capillary Electrophoresis
Different forms in the Market
rhEPO production in Roller Bottle Incubator
Epoetin zeta
Darbepoe tin
MethoxyPEGEpoetin beta
Biopoin (CT Dynepo Arzneimittel Repotin (Shire)(Bioclones ), Eporatio unfavorable and Ratioepo ), EPOMAX market (Ratiopharm (Baxter) conditions )
Silapo (Stada)
Aranesp (Amgen)
Mircera (Roche)
Epoetin beta
Clinical use (Brand names)
Epogen (Amgen), Procrit (JanssenUS), Eprex (Janssennon-US), Erypo, ESPO (Kirin)
Recormon(RocheUS), NeoRecormon (Rochenon-US), Epogin (Chugainon-US)
Cell substrate of origin
Chinese hamster ovary Cell
Chinese hamster ovary Cell
baby hamster kidney cells
Human cell line
Chinese hamster ovary Cell
Terminal half life
6–9 hr
6–9 hr
6–9 hr
6–9 hr
6–9 hr
6–9 hr
25hr
130–140 hr
Mass (Dalton)
30.4
30.4
