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Comparison of FBS and Other Bovine Serums

Fetal bovine serum (FBS) is  the most widely used growth promoter used in cell culture. FBS contains more  growth factors than any other animal serum, and also has lower levels of  undesirable complements than other types of serum. FBS is also the most expensive  and difficult to source serum, with prices ranging from 3x - 10x more than  other bovine serum products. Growing demand, coupled with a lower supply  of FBS has resulted in a volatile market for US FBS and consequently prices  have increased significantly in the past few years. You can read more about the  supply and demand of US FBS on RMBIO’s Expressions using this link: With the increase in US FBS prices, we have  seen an increase in demand for other bovine serum products, including newborn  and calf serum. This article provides a comparison among classifications of  bovine serum.

The classification of  bovine serum is determined based on the age of the animal from which the serum  is collected. Industry standards classify US bovine serum according to the  following guidelines:

  • Newborn calf Serum, less than 14 days
  • Formula Fed Calf Serum, less than 22 weeks
  • Calf Serum, 3 weeks to 12 months
  • Adult Bovine Serum, greater than 12 months

Newborn calf serum and calf  serum are cost effective alternatives to FBS, and we see them used in  situations where large quantities of serum are used, such as fermentation  processes and vaccine production. Research and diagnostic users of bovine serum  often consider non-FBS options for their cell culture medium as well. Newborn  calf serum and calf serum are most often used in situations where the cell line  is robust and thus less demanding. 

Total protein levels, IgG,  and endotoxin, along with price, are the most common attributes our customers  consider in their evaluation of serum. The following chart shows the typical  values for these important serum components from lots of serum we have manufactured  in the past several years. 

Total  protein and IgG (gamma globulin) levels in bovine serum increase with the age  of animal the serum is collected from. The USP guidelines specify that total  protein levels in FBS are less than or equal to 4.5g/dL, but the standards do  not call out protein specifications for the other categories of bovine serum. 

The total protein in serum is measured by taking a chemistry panel of the serum. While there are numerous proteins in bovine  serum, the most abundant is bovine serum albumin (BSA). Some serum  applications, like vaccine production, require a reduction or complete removal  of bovine protein from the final product. In those instances lower levels of protein  make for less work which is one reason RMBIO has seen an increase in newborn  calf serum demand recently. Historically newborn calf serum has been priced  enough higher than calf serum that many users opted to spend the additional  resources removing the extra protein in order to realize the cost savings.  This cost-benefit analysis has changed  recently though as market dynamics have caused the price of calf serum higher  than newborn. 

IgG levels  increase significantly from FBS to the other bovine serum products. Some serum  users work to reduce IgG levels in order to eliminate interference, others purchase serum that has been further manufactured using proprietary chromatography techniques that result in low IgG FBS.  To learn more about Low IgG FBS follow this link: 

Endotoxin levels are largely impacted by the collection methods, equipment used in the  serum collection and the efficiency of the serum filtration. Endotoxin levels  are measured with a LAL gel clot assay that uses horseshoe crabs, although there is some  momentum building for the use of PTS chromogenic readers to measure endotoxin levels of serum.

Most  customers end up sampling lots of serum before making a determination of which  lot to purchase. The decision to use a non-FBS bovine serum is largely a  determination of cost-benefit of the growth promotion versus of the cost. While FBS remains the most popular choice of bovine serum in terms of sheer numbers  of users, RMBIO has seen a shift in the percentages of our customers sampling  and ultimately purchasing other options like newborn calf serum, calf serum and Fetalgro. Understanding some of the differences among the serum options may  help users decide if one they should consider testing one or more of the  alternatives to FBS that RMBIO manufactures.