Abstract
Monoclonal antibodies (MAb’s) have become one the most powerful therapeutic and diagnostic tools in modern medicine. Some estimates target the worldwide market of MAb’s on the order of $125 billion in the next four years. Recent advances in molecular biology, immunology, and development of robust production platforms will drive the development of more MAb’s suitable to treat an ever increasing number of disease states. This circumstance combined with the fact that many of the original antibody therapies from the 1980s and 1990s will soon be coming off patent will attract a great deal of investment in the development of larger industrial facilities to increase monoclonal antibody to meet increasing demand. In this review, the present state of the science that underlies the development of new antibodies therapies in Chinese hamster ovary cells combined with a description of the present challenges facing the industry in terms of the limitations of output and compliance with current good manufacturing practices and FDA regulations. Also addressed are future challenges to overcome production bottlenecks, description of critical quality control attributes particular to antibodies, and detailed treatment of scale-up considerations.
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Abbreviations
- pDO:
-
Percent dissolved oxygen
- \(\hbox {pCO}_{2}\) :
-
Percent dissolved \(\hbox {CO}_{2}\)
- HPLC:
-
High performance liquid chromatography
- RP-HPLC:
-
Reverse phase-high performance liquid chromatography
- CHO:
-
Chinese hamster ovary
- MAb:
-
Monoclonal antibody
- MTX:
-
Methotrexate
- MeOH:
-
Methanol
- ACN:
-
Acetonitrile
- HGPRT:
-
Hypoxanthine-guanine-phosphoribosyl-transferase
- HAT Medium:
-
Hypoxanthine-aminopterin-thymidine medium
- MALDI:
-
Matrix-assisted laser desorption/ionization
- MALDI-TOF:
-
Matrix-assisted laser desorption/ionization-time-of-flight
- CEX:
-
Cation exchange chromatography
- AEX:
-
Anion exchange chromatography
- IEC:
-
Ion exchange chromatography
- HIC:
-
Hydrophobic interaction chromatography
- ELISA:
-
Enzyme linked immunosorbent assay
- FT-ICR:
-
Fourier ion cyclotron resonance
- DHFR:
-
Dihydrofolate reductase
- GS:
-
Glutamine synthase
- IgG:
-
Immunoglobulin G
- TFF:
-
Tangential flow filtration, spin filter
- ATF:
-
Alternating tangential flow
- ESI:
-
Electrospray ionization
- FT-ICR:
-
Fourier transform ion cyclotron resonance
- LTQ-Orbitrap:
-
Hybrid linear quadropole ion-trap-orbitrap
- DFPS:
-
Depth filter perfusion system
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Gaughan, C.L. The present state of the art in expression, production and characterization of monoclonal antibodies. Mol Divers 20, 255–270 (2016). https://doi.org/10.1007/s11030-015-9625-z
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DOI: https://doi.org/10.1007/s11030-015-9625-z