Bovine serum is the liquid fraction of clotted blood, obtained from an ox (Bos taurus, among others), that has been depleted
of cells, fibrin, and clotting factors. Since the advent of modern cell culture, manufacturers of biological products have used
bovine serum extensively as a cell culture growth supplement. Its rich nutritional composition of proteins, growth factors,
hormones, amino acids, vitamins, sugars, lipids, trace elements, and other components supports a broad range of cell culture applications in research and commercial manufacture of vaccines, natural source and recombinant biologics (hereafter biologics), engineered tissues, and other emerging cell-based therapeutic products intended for human or veterinary use. The predominant type of serum used in research applications is Fetal Bovine Serum (FBS). Calf serum (from newborn and older animals) is used much less frequently, but because of its lower cost it may be widely used in commercial manufacturing.
As is the case with other animal-derived products, bovine serum carries a potential risk of introducing extraneous agents into cell culture. Serum manufacturers and regulators must adopt rigorous sourcing and testing procedures and strict processing and production guidelines to ensure the quality of bovine serum.
The objective of increasing the quality and safety of biologics produced with bovine serum, coupled with attempts to mitigate regulatory burden, have caused developers to investigate alternatives to serum supplementation, resulting in
application-specific serum-free medium formulations. Although it is recognized that bovine serum should be avoided when
there is an option to use serum-free medium, there are cases where this is technically impossible or impractical.
This chapter describes issues related to sourcing, production, and characterization of bovine serum to ensure its safe use. A
list of relevant regulatory and guidance documents is presented in Appendix 1. Serum manufacturers and serum end users
(manufacturers of biological products) should consider and apply as needed the controls and procedures outlined in this chapter to ensure the safe use of bovine serum components in research and pharmaceutical manufacturing.
Bovine blood should be processed and serum separated (harvested) in such a way as to minimize bacterial and mycoplasmal contamination, which in turn minimizes endotoxin levels in serum product. Gentle, quick blood processing helps to minimize hemolysis, further enhancing the quality of the serum product. After collection, blood is first allowed to clot for a specified period of time and under controlled conditions, then centrifuged in a refrigerated centrifuge. Serum is then removed from the clot, typically by centrifugation; pooled and mixed in a pooling vessel; transferred to labeled containers; and frozen, unless it is filter-sterilized immediately. Serum manufacturers should describe each process step and carry out serum processing activities,including sample collection and in-process quality control testing, following the manufacturer’s approved procedures.
