Effect of cell culture medium components on color of formulated monoclonal antibody drug substance
| Autor: | Boyan Zhang, Natarajan Vijayasankaran, Robert Kiss, Steve Meier, Yi Yang, Amy Lim, Martin Gawlitzek, Feng Li, Sharat Varma, Melissa Mun, Silvana R. Arevalo, Trevor E. Swartz |
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| Rok vydání: | 2013 |
| Předmět: |
Drug
Pyridoxal genetic structures medicine.drug_class media_common.quotation_subject Iron Riboflavin Cell Culture Techniques Color CHO Cells Monoclonal antibody Bioreactors Cricetulus Folic Acid medicine Animals Food science media_common High concentration Chromatography biology Chemistry Color intensity Drug administration Antibodies Monoclonal Pyridoxine Chromatography Ion Exchange Process conditions Culture Media Vitamin B 12 Cell culture Vitamin B Complex biology.protein Antibody Biotechnology |
| Zdroj: | Biotechnology progress. 29(5) |
| ISSN: | 1520-6033 |
| Popis: | As the industry moves toward subcutaneous delivery as a preferred route of drug administration, high drug substance concentrations are becoming the norm for monoclonal antibodies. At such high concentrations, the drug substance may display a more intense color than at the historically lower concentrations. The effect of process conditions and/or changes on color is more readily observed in the higher color, high concentration formulations. Since color is a product quality attribute that needs to be controlled, it is useful to study the impact of process conditions and/or modifications on color. This manuscript summarizes cell culture experiments and reports on findings regarding the effect of various media components that contribute to drug substance color for a specific monoclonal antibody. In this work, lower drug substance color was achieved via optimization of the cell culture medium. Specifically, lowering the concentrations of B-vitamins in the cell culture medium has the effect of reducing color intensity by as much as 25%. In addition, decreasing concentration of iron was also directly correlated color intensity decrease of as much as 37%. It was also shown that the color of the drug substance directly correlates with increased acidic variants, especially when increased iron levels cause increased color. Potential mechanisms that could lead to antibody coloration are briefly discussed. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1270–1277, 2013 |
| Databáze: | OpenAIRE |
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