Advances in Animal-Free Manufacturing of Biopharmaceuticals - New recombinant raw ingredients developed for use in large-scale mammalian cell culture are becoming readily available. - BioPharm

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Advances in Animal-Free Manufacturing of Biopharmaceuticals
New recombinant raw ingredients developed for use in large-scale mammalian cell culture are becoming readily available.


BioPharm International



Figure 1. Combined results from subculture experiments showing the percentage cell growth with DeltaFerrin-supplemented serum-free media relative to growth obtained with holo human transferrin and other commercially available chemical chelators (ferrous ammonium sulphate, ferrous sulphate, and Invitrogen B), over five subcultures in Vero-PP, Madin-Darby canine kidney (MDCK), and baby hamster kidney (BHK)-21-PP1-C16
LONGR3 IGF-I is a recombinant insulin-like growth factor (IGF-I) analogue manufactured in E. coli Studies comparing the effectiveness of LONGR3 IGF-I with insulin for sustaining cell growth and viability in serum-free CHO cell cultures have found that recombinant LONGR3 IGF-I protein is better able to sustain viability under production conditions than is insulin.8 Insulin is mostly used at supra-physiological concentrations, and its ability to promote growth and survival is attributable to its activation of the IGF-I receptor at these high concentrations. LONGR3 IGF-I is also more potent than insulin at activating the IGF-I receptor, even at 200-fold lower concentrations in both CHO and HEK293 cells (Figure 1).11

Recombinant Transferrin

Animal- and human-derived transferrins have traditionally been used as cell culture supplements to facilitate optimal iron metabolism. Studies in CHO cells have found that a combination of both IGF-I and transferrin is necessary to maintain viability and proliferation upon the withdrawal of serum from the culture media.12


Figure 2. Combined results from subculture experiments showing the percentage cell growth with DeltaFerrin-supplemented serum-free media relative to growth obtained with holo human transferrin and other commercially available chemical chelators (ferrous ammonium sulphate, ferrous sulphate, and Invitrogen B), over five subcultures in Vero-PP, Madin-Darby canine kidney (MDCK), and baby hamster kidney (BHK)-21-PP1-C16
In an effort to move away from animal-derived transferrins, investigators look to using combinations of chemical-based iron chelators. However, a recent study questioned the ability of the chelators to consistently support a wide range of cell lines in serum-free media. Additionally, in comparing various commercially available iron chelators (ferrous ammonium sulphate, ferrous sulphate, and Invitrogen B) against a plasma-derived recombinant human transferrin (DeltaFerrin), the authors found that the recombinant human transferrin (DeltaFerrin) was the only alternative growth factor that showed almost equal potency to native human holo transferrin over five subcultures in Vero-PP, MDCK, and BHK-21-PP1-C16 (Figure 2).9

The use of chemical chelators for industrial-scale manufacturing may also be limited by the chelators' unpredictability in controlling and managing the redox cycle and cell oxidation processes. An animal-free recombinant human holo transferrin, specifically designed and manufactured for industrial cell culture applications, provides the benefits of natural plasma-derived transferrin, with the defined, regulatory-friendly aspects of chemical alternatives.


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