Serum in Cell Culture

Fetal bovine serum (FBS) is the most widely used medium supplement for the in vitro cell culture of eukaryotic cells. Other bovine sera include newborn calf (from calves under 3 weeks old), cadet calf (< 6 months old), calf serum (<12 months old), adult bovine serum (<12 months), and donor bovine (<36 months old). Serum is the blood fraction remaining after the coagulation of blood, followed by centrifugation to remove any remaining blood cells. Traditionally, serum is a necessary supplement for many classical medium formulations such as DMEM, MEM, RPMI and others. Newer, serum-free media can support the growth of most cell types without the need for serum.

Challenges with Serum Use in Cell Culture

Serum is an ill-defined and variable mix of nutrients, proteins, growth factors, attachment factors, hormones, and trace elements. Bovine serum albumin (BSA), transferrin and insulin are major functional components of serum. Fetal bovine serum is typically favored among sera since it contains higher levels of substances that promote cell growth and reduced levels of certain other molecules, including immunoglobulins (IgG, IgM) that may interfere with some bioproduction applications. Approximately 700,000 liters of serum are used annually for cell culture.

Animal sera are commercially available from many manufacturers that harvest serum from cattle slaughterhouses. Because the performance of serum in cell culture is variable from batch to batch, batches are usually tested by the end user for suitability for the specific cell type. Cells may require adaptation when switching between batches of serum.

Although serum is used extensively by life science researchers, it has become a source of concern for EMA and FDA regulated products being commercialized as biopharmaceuticals mainly due to the risk of contamination from adventitious pathogens of animal origin. European regulations tend to be the most strict with regard to the elimination of animal components including serum from cell culture processes. This is due to the continent’s history with bovine spongiform encephalopathy (Mad Cow Disease) and the human equivalent, Creutzfeldt-Jakob Disease.

Reagents and Methods for Reducing or Eliminating Serum from Cell Culture

Because of the complexity and variability of an ingredient like serum, reducing or eliminating it from cell culture media can seem like a daunting challenge. Not only are the right recombinant, animal-free raw materials such as Cellastim™ recombinant albumin, Optiferrin™ recombinant transferrin, ITSE, and Zap-SR important, but a working knowledge of how to use these reagents is critical for the successful development of high performance animal origin free medias.

In addition to our line of well-defined, animal-free products, InVitria offers several media development strategies to assist anyone who is interested in transitioning to a completely animal free media. Our media experts can provide technical expertise in your media development projects via step-by-step instruction or co-development in InVitria’s laboratory. Our media development team’s experience and knowledge will combine to provide customized assistance that will help you to establish cell culture media formulations that fit your needs. For more information, e-mail our media experts at


  1. Barnes, D., Sato, G. (1980). Serum-free cell culture: a unifying approach. Cell. 22(3):649-55
  2. (2012). FDA Issues Guidance for Warning Labels on All Drugs Produced Using Blood Products including Plasma-derived Albumin
  3. European Medicines Agency (EMA). (May 2013). Guideline on the use of bovine serum in the manufacture of human biological medicinal products. EMA/CHMP/BWP/457920/2012 rev 1.
  4. Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (FDA/CBER). (June 2012). Guidance for Industry: Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products (PDF – 318KB)
  5. Gstraunthaler, G. (2003) Alternatives to the use of fetal bovine serum: serum-free cell culture. ALTEX, 20(4):275-281
  6. International Serum Industry Association. Frequently asked Questions-Bovine Serum
  7. National Institutes of Health (NIH). Creutzfeldt-Jakob Disease Fact Sheet.
  8. Price, P, Gregory, D. (1962) Relationship between in vitro growth promotion and biophysical and biochemical properties of the serum supplement. In Vitro. 18:576-584.
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