The Advantages and Disadvantages of Serum

Serum, as the supernatant from clotted blood of bovine or equine sources has been found to
provide high growth-promoting activity for a range of mammalian cell lines. This is a rich source of
often unidentied components such as attachment factors, micronutrients, trace elements, water
insoluble nutrients, growth factors, hormones, proteases, and protective elements (antitoxins,
antioxidants, antiproteases), not provided by the basal medium and that promote rapid cell growth.
Furthermore, the high albumin content of serum ensures that the cells are well-protected from
potentially adverse conditions such as pH uctuations or shear forces, which may occur particularly
in large-scale cultures. However, supplementation of culture media with serum has many inherent
disadvantages.

(a) Batch-to-batch variation in composition. The composition of serum is variable and undened,
which leads to inconsistent growth and productivity. Each batch of serum can vary in composition
depending upon the diet and environmental conditions of the donor animals. This variation can
cause signicant differences in the growth-promoting characteristics of the serum, and ultimately
causes signicant differences in productivity of the cell-culture process.

(b) A high protein content that hinders product purication. The cells grown in a bioreactor secrete
the product of interest (normally a protein) into the culture medium. If the culture medium contains
serum, its protein concentration is already high. This causes difculties in purication of the nal
product. Culture medium with a serum content of 10 % v/v has a high protein concentration that
approaches 10 g/L. In comparison, the concentration of a recombinant protein secreted by the cells
may only reach 0.1 g/L. This poses a problem in the purication process of the targeted protein
within a large mix of serum protein. Furthermore, if the target is a specic monoclonal antibody, it
may well be mixed with any other non-specic antibodies present in the serum and these are very
difcult to separate.

(c) The potential for product contamination. The threat of contamination arises from unwanted
viruses and mycoplasma that may be present in serum as well as the vectors of bovine spongiform
encephalopathy (BSE, or Mad Cow Disease). Although there have been no proven cases of such
contamination getting into the nal product, no one wants to take the chance of manufacturing
biopharmaceuticals that may have had contact with unknown agents of disease (Merten 2002).
Prions as agents of BSE are of particular concern because of the difculty of their removal. The
incidences of new variant CJD (the human version of BSE) that have occurred in Europe are a great
source of concern for the vaccine industry that has used serum and for which there is up to now no
ideal substitute. Because of the concern over the potential human consequences of the presence of
these contaminants in therapeutic products, most regulatory authorities have demanded the use of
serum-free processes for biopharmaceutical manufacture.

(d) Cost and availability. Fetal bovine serum (FBS) is often regarding as the best available serum
supplement for supporting cell growth. However, the cost is often prohibitive at $5001,000 per litre
and this can account for up to 95 % of the overall cost of the media. The most desirable source of
FBS is from countries that have had minimal incidences of BSE such as New Zealand. However,
there has from time to time been a global shortage of this serum and this can cause a problem in the
continuity of a bioprocess.

(e) Ethical concerns. There is an increasing concern for the ethical treatment of animals that
includes standard procedures needed to obtain serum from a bovine fetus.