Frequently ASKED QUESTIONS
FREQUENTLY ASKED QUESTIONS
Given that the death of some pregnant animals is unavoidable, the fetus can be used to serve science, and generate jobs. This contribution benefits research and development and should not be underestimated.
The collection of the blood is done without causing pain to the fetus. The fetus’s life ends through oxygen depletion, generally agreed to be a gentle method of life termination. Cell culture technology can reduce the use of live animals in science. Research is also being done to produce meat by cell culture, which could ultimately lead to the end of breeding animals for food.
The slaughtering of pregnant animals is, in most cases, an unplanned event. The frequency depends on farming techniques. In most cases, the condition of gestation is unknown; especially where animals are produced naturally; in the case of cattle moving freely around, grass fed, heifers and steers together. No cows are killed with the main purpose of harvesting the fetal blood. The blood is collected as a by-product from cattle slaughter operations for the bovine meat. The pregnancy condition is unknown when an animal enters the slaughtering line. The percentage of pregnant cows going to slaughter is very low and decreasing year by year as cattle farming techniques constantly improve.
Fetal Bovine Serum
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.
Animal Serum and Plasma
The serum’s source is from a USDA Approved country. This means that serum is produced from blood collected in countries that have been approved by the United States Department of Agriculture (USDA) to export ruminant serum products to the United States. Eligible countries that export fetal bovine serum into the U.S. include Australia, Canada, Chile, Costa Rica, El Salvador, Guatemala, Honduras, Mexico, New Zealand, Nicaragua, and Panama.
Maintaining cells in vitro in a healthy condition and over time is a complex task. They will only survive, grow and multiply if they are well fed and provided with an appropriate and protective environment. Complex mixtures of substances (“media”) are used to bathe the cells in order to both feed and protect them. Different cells have different requirements. In many instances the presence of serum in the mixture is essential if the cells are to grow adequately and normally. Bovine serum is much the most widely used, because high quality bovine serum is available in sufficient volume and has been found to support cell growth very well indeed.
Bovine serum is a by-product of the meat industry. Bovine blood may be taken at the time of slaughter, from adult cattle, calves, very young calves or (when cows that are slaughtered are subsequently found to be pregnant) from bovine fetuses. It is also obtained from what are called “donor” animals which give blood more than once.
Blood is available from bovine fetuses only because a proportion of female animals that are slaughtered for meat for human consumption are found (often unexpectedly) to be pregnant.
Bovine serum is categorized according to the age of the animal from which the blood was collected as follows:
Serum is the centrifuged fluid component extracted from either clotted or defibrinated whole blood. The bovine serum comes from blood taken from domestic cattle.
Whilst the procedure of making serum may seem to be straightforward, the processing of serum takes place under very tightly controlled conditions. The process has been carefully developed and uses sophisticated facilities and equipment, and is accompanied by extensive testing particularly stringent when processed bovine serum is intended for use in the production of medicinal products.