There are some cell lines-specific serum-free alternatives available. In most cases, cell adaptation is needed, yields are lower and costs are higher.

Fetal bovine serum (FBS) is essentially a biological product. All fetal bovine serum batches are unique, with specific characteristics, different from all other batches.

The demand for FBS is growing along with the latest research developments, including stem cells, cell therapy, new vaccines and proteomics.

The availability of FBS is diminishing. Meat and calf prices are increasing as consumers in some countries increase the consumption of beef; and as cattle breeding techniques are permanently improving. These combined factors lead to a reduced frequency of pregnant cows at slaughter. The collection of FBS in new countries has, for many years, compensated for the decrease in supply; but now there are no more new producer countries available. The present world supply of FBS is short and will continue decreasing.

Fetal Bovine Serum imports into the EU are less restricted than in the USA. A proposal made by USDA in 1994 to apply the same FBS import policies as the EU did not get support from the US FBS industry. The International Serum Industry Association (ISIA) supports efforts to harmonize import rules, suggesting compliance with the OIE recommendations. In the meantime, FBS in the USA remains more than twice as expensive as in Europe.

The serum’s origin has no influence on cell growth. Biosera has compared cell growth in FBS from seven different countries on three continents, and confirmed that regardless of the country of origin, all cell lines tested had the same average performance. One batch of FBS may work well for one specific cell line, but not for another. “Serum quality” is specific for each cell line. That is why testing of FBS is widely used when dealing with sensitive cell lines. Biosera performs the most extensive analysis of biochemical parameters and testing on cell lines in the industry, making available the results on the Certificates of Analysis.

A huge price difference exists between countries classified as “FMD-Free-without-vaccination” for which demand exceeds supply, and countries listed as “FMD-Free-with-vaccination” where supply historically has exceeded demand. The price difference has been several hundred per cent, whereby serum users in the US have paid billions of USD more than serum users in the EU. Proposals from USDA to harmonize US and EU import rules for FBS relating to FMD (following OIE guidelines), have repeatedly been turned down by the US serum industry.

Wrong beliefs about risks associated to BSE have lead some FBS providers to promote the Australian origin as “safer” without any scientific basis, making this origin several times more expensive than any other. The Australia “safer” status is being promoted, despite the virus status of Australia; and despite the higher risk of misrepresentation associated with such huge price differences.

The price differences persist due to longtime marketing efforts promoting certain origins, and regulations limiting trade, even among countries that according to the OIE’s classification have identical veterinary risk status (regarding viruses of import concern for FBS). ISIA has among its objectives the education of serum users, and EU and USA are working to harmonize trade rules, all of which will contribute to harmonizing price levels for most FBS origins.

Australian fetal bovine serum prices are higher because Australia is perceived to be a ‘safer’ origin for BSE and cattle viruses. Canada and Australia were the first countries outside the USA where fetal bovine serum was produced. In the 1980s, BSE cases that occurred in North America became a strong argument in favour of the Australian fetal bovine serum. The point was made that being “isolated”, Australia was necessarily the most secure origin.

However, BSE has never been found in young animals, let alone in fetuses, and BSE transmitted by animal feed has been eradicated. The remaining BSE cases are spontaneous BSE events, which occur in all cattle populations (Stanley B. Prusiner, Nobel Prize 1997). All countries find spontaneous BSE cases if their sanitary surveillance systems are sensitive enough. Additionally, the OIE veterinary authorities have declared all blood and blood products, regardless of country of origin, to be safe in terms of BSE. So, the BSE arguments in favour of Australia were clearly ill-founded from the beginning, and have become obsolete.

Nevertheless, Australian fetal bovine serum is still sold as ‘safer’, at much higher prices than other origins. Paradoxically, Australia is actually among the countries with the most types of viruses of import concern, including Blue Tongue, Akabane, Aino, and Bovine Ephemeral Fever (see FAQ #13). Like in the tale “The Emperor’s new clothes”, by Danish writer Hans Christian Andersen, those who believe that paying more will assure them a better serum, are being misled.

FMD is relevant for regulatory import purposes but not for cell growth. The USA and a few other countries only allow FBS imports from countries free from FMD, WITHOUT vaccination while most other countries also accept FMD-free WITH vaccination. Both types of FMD-free countries are free of FMD cc and circulating FMD viruses, as verified by the OIE and declared equally safe.

Some cattle viruses can cross the placenta of the cow and infect the calf fetus, thus contaminating FBS and potentially making it unsuitable for use in cell culture. Some of these cattle viruses have a limited distribution and only exist in certain parts of the world.  These are viruses of concern when importing FBS from infected countries – See Table of Diseases of Importation Concern for FBS. Other cattle viruses exist in all countries, and regardless of country of origin, the FBS must be tested or treated to assure freedom from these and other viruses (See USDA 9 CFR 113.53 and EMEA-CPMP-BWP-1793-02). The treatment of choice for most FBS is gamma irradiation at 25-45 kGy to guarantee freedom from viruses.

Fetal Bovine Serum is collected from the fetuses of pregnant cows, and slaughtered in compliance with the OIE (World Animal Health Organization) guidelines and internationally accepted standards of veterinary inspection.

There is a wide range of applications for fetal bovine serum. The most important is in the field of biopharmaceuticals and vaccines. It is used in the research, manufacture and control of human and veterinary vaccines and of drugs, many of which are at the cutting edge of drug development.

Fetal bovine serum is also used extensively in research. A technique known as “Cell culture” is widely applied in the manufacture of both vaccines and bio-pharmaceuticals in which bovine serum is broadly used.

Fetal Bovine Serum (FBS) comes from the blood drawn from a bovine fetus via a closed system of collection at the slaughterhouse. Fetal Bovine serum is the most widely used serum supplement for the in vitro cell growth factors because of its high content of embryonic growth promoting factors.

The serum should be stored frozen and protected from light. The recommended storage temperature is -10°C to -40°C. At temperatures below -40°C, the bottles may become brittle increasing the risk of breakage.

Serum may be stored between +2 to +8°C for up to 8 weeks without diminishing its performance (*).
Internal studies in Biosera have shown that during 26 weeks of storage (between +2 and +8°C) the serum’s capacity to promote cell growth was not significantly altered.
(*) Art to Science, Vol.19, No.2, “Serum Stability at Refrigerated Temperatures (2-8°C).

Some preparations of trypsin contain phenol red. Since the product is shipped with dry ice, there could be a significant CO₂ build up in packaging. This CO₂ may enter the solution and lower the pH slightly, giving an orange (around pH 6.5) vs. pinkish (around 7.3) color. The solution, if orange (acidic) can still be good to use as is, or sodium hydroxide may be added to adjust the pH.