ADVANCES IN RECOMBINANT PROTEIN ALTERNATIVES
With the construction of further barriers to the use of animal-derived materials, there are growing needs and trends in the
industry to move toward the use of serum-free, chemically defined, and most recently, protein-free media formulations for
use in mammalian cell culture. Using chemically defined media components not only reduces the risk of introducing adventitious
agents, but it also assists both upstream and downstream process optimization.
While major advances have been made in this area, there are still drawbacks to the use of these products, especially for industrial-scale
culture.5,6,7 Transfer to serum-free or protein-free media can be very stressful for cells, and it typically requires a period of adaptation
or "weaning." Successful adaptation can be time-consuming and cell-line-dependent, and a lack of protein components can lead
to a less robust and less reproducible process.
It is recognized that the addition of specific growth factors and proteins (which are naturally found in serum) can enhance
cell viability and productivity. Serum-free media, which is still used extensively in research laboratories, can contain proteins
that may or may not be animal- or human-derived. Similarly, to enrich protein-free media, hydrolysates may be added that are
not always non-animal in origin.
Recently, dedicated research and development into the production of defined, recombinant alternatives to three critical components
of serum (insulin, transferrin, and albumin) have led to a range of animal-free recombinant protein ingredients that are designed
and manufactured specifically to optimize mammalian cell growth and productivity at the industrial scale. With these ingredients,
researchers should now be able to achieve the performance associated with protein-supplemented media while avoiding the associated
risks of traditional animal-derived supplements.
Studies with recombinant ingredients have shown equivalent or improved performance in a wide range of cell types up to commercial
scale.8,9,10 Manufactured to recognized quality standards and offering continuity of supply, these ingredients provide the confidence
in critical raw material quality that is required of products used in long-term biopharmaceutical manufacturing.
Recombinant Insulin-Like Growth Factor
Growth factors are essential for long-term growth and proliferation of cell lines in serum-free media formulations. Recombinant
therapeutic insulin has been used as a growth factor in serum-free cell culture. However, its primary use for the treatment
of diabetes has led to supply and availability issues for cell culture users.
Recombinant insulin-like growth factors are now available as a dedicated raw material, manufactured exclusively for the industrial
cell culture market. Studies using this mitogen as a supplement in cell culture have shown that it results in performance
that is equivalent to or better than recombinant insulin in numerous cell types, including: Chinese hamster ovary (CHO), baby
hamster kidney (BHK), human embryo kidney-293 (HEK293), Vero, PER.C6, Madin-Darby canine kidney (MDCK), and fibroblasts (data