Serum and its use for research and in the production of diagnostic kits, vaccines and biotherapeutic molecules
Serum is primarily supplied as a by-product of the meat industry. Serum products are typically classified based on the age of the animal at the time of serum collection. Bovine serum products include: fetal bovine serum (FBS); newborn calf serum; calf serum; and adult bovine serum. A smaller portion of adult bovine serum is obtained through the use of donor animals.
Serum for Cell Culture
Serum products have been used for several decades in cell culture. Serum provides a close representation of what cells would obtain in the body. Key components of serum for cell health and growth include albumin, transferrin, growth factors, amino acids, vitamins, minerals, and various other nutritive and protective factors. Fetal bovine serum, a bovine serum product, is widely accepted as the gold standard for cell culture by which other serum-free and chemically-defined formulations are compared.
Serum production begins with the collection of blood; material is then chilled & centrifuged to extract the raw serum and frozen. To process the raw serum into a finished product for the end customer, a sterile filtration then must be completed. Serum is also available that has undergone heat inactivation or gamma irradiation to reduce possible viruses. Serum suppliers typically test their product for endotoxin level, viruses and performance in cell culture. Customers, particularly ones buying large lots of FBS, will also conduct testing on the serum usually focused on cell culture performance
The largest consumers of serum are the United States and Europe. As such, each has its own requirements and regulatory bodies that oversee the importation of serum. In the United States, the United States Department of Agriculture (USDA), oversees the importation of serum into the United States and monitors evolving situations that may affect importation from certain countries.
The World Organization for Animal Health (OIE) is an international body that evaluates animal disease and health standards. BSE, the virus that causes mad cow disease, is monitored closely by OIE to ensure that the level of risk of cattle BSE transmission is accurate. There are three possible designations that a country could receive from OIE pertaining to BSE risk:
- Negligible BSE risk – The country has a very low risk that cattle raised there will transmit BSE.
- Controlled BSE risk – The country has put procedures and testing in place to minimize the risk of transmitting BSE.
- Undetermined BSE risk.
In May 2013, OIE upgraded the United States BSE risk from controlled BSE risk to negligible BSE risk. Countries must meet a number of stringent criteria to be in this category. There are 22 other countries in this category including Australia and New Zealand. This new reclassification from the United States broadens FBS options to the growing scientific community.
Another organization involved in serum is the International Serum Industry Association (ISIA), who serves as an industry association and is made up of member companies that are involved in the serum industry. ISIA provides guidelines and industry best practices. They have also recently instituted an ISIA Quality Seal, where serum suppliers can undergo an audit process to ensure that they have traceability back to the original farm or abattoir where the serum is collected. This seal then tells customers that a third party has verified that these companies have the appropriate traceability and that their products are not adulterated. However, most leading serum suppliers should be able to provide this traceability on their own during a supplier audit.
Serum is a commodity product and as such there can be much variation in pricing over time based on factors such as the meat industry, weather, natural disasters, the economy and as in any commodity product – demand. The cost of FBS has been on the rise since mid-2012 and will continue to rise in 2014. This kind of price fluctuation is inevitable based on its commodity nature. Other factors that can cause variations in pricing of specific serum products are the differences in testing, quality, source of material and other treatments, i.e. heat inactivation and/or gamma irradiation.
Considerations for Choosing a Serum Product
When choosing a serum product it is important to consider the type of research that is being conducted, the sensitivity of the cell line to things like endotoxins, and whether the product is going to be used in clinical manufacturing. Each scenario will dictate the quality level of the serum needed to successfully operate and the subsequent product pricing. Below I have sketched out a few differences in serum product categories based on quality, testing and origin differences. I have assigned my own names and general information for each category to give readers an idea of the types of differences. While not exactly the same, most suppliers will have products that fall into these types of categories. Each supplier has different products to meet customer needs and may have more specific variations, quality levels and testing options available then I have listed here and as a result they will not match my categories exactly. However, my goal is to provide the reader with a basic understanding of how the quality of serum can be different and when you might use each type.
This describes a good serum for basic research that is less expensive and has a higher endotoxin level than other higher quality serum. This is a perfectly acceptable choice if you are not working with a finicky cell line and you aren’t using the product for clinical or pharmaceutical manufacturing purposes.
This describes a product that is also for research, is a bit more expensive, and has a lower endotoxin level. This type of product may be preferable to difficult cell lines. This is a better product to use in research if you have a difficult cell line that is more sensitive to variations including endotoxin, but is also not appropriate for clinical or pharmaceutical manufacturing purposes.
This is a product that is designed for clinical manufacturing or very sensitive research. It has low endotoxin levels and can have additional screenings and/or treatments including extras like BVDV screening, heat inactivation, gamma irradiation or others. It is also usually from negligible BSE risk countries and is sometimes sourced from donor bovine serum instead of as a by-product. This product is the most expensive type of serum and for good reason. It provides a higher level of quality and assurance designed for pharmaceutical manufacturing purposes.
In addition to the product grade, customers should also carefully consider the supplier from where the serum is being obtained. Unless the customer is planning on doing extensive quality and traceability studies, then they will need to rely on the supplier’s quality assurances. To assist customers, factors including the company’s reputation or perhaps the ISIA seal could be used to ascertain serum quality prior to purchase. I have also listed below things I believe should be taken into consideration before purchase:
- Don’t let a lower cost product make you overlook quality. As the saying goes, if it looks too good to be true, then it probably is.
- Serum that is blended from multiple regions can be problematic and traceability in these situations can be a challenge.
- Serum suppliers should be able to trace their serum back to the original farm or abattoir where the serum was collected to ensure traceability.
- The product should not be adulterated with any other ingredients.
- Examine each supplier’s basic testing and choose accordingly.
- Be sure your supplier understands the regulatory requirements in the US and Europe and seek their assistance in finding a serum that meets your needs.
Major suppliers of serum products include Gibco (Life Technologies), HyClone, Sigma Aldrich, Gemini Bio-Products and Atlanta Biologicals.