How We Define Our Culture Media and Supplements

Choosing a cell and tissue culture medium is a critical step in ensuring the quality and performance of your cultures. For cell therapy manufacturers, this choice can also affect the safety of your cell therapy. With the wide selection of culture media available, it is essential to have clarity on how each supplier defines their culture media and to understand the associated implications for product performance, safety, and compliance.


Definitions for Our Media and Supplement Formulations

Our cell culture media and supplements are available in a variety of different formulations. The formulation you choose will depend on your intended application and any regulatory compliance requirements.

For more information on specific products or for assistance with choosing a culture medium for your application, please contact Product & Scientific Support at techsupport@stemcell.com.

Protein-Free

  • Does not contain proteins or polypeptides as ingredients.
  • May contain free amino acids, dipeptides, or tripeptides derived from non-animal sources.
  • May contain plant, yeast, or bacterial hydrolysates.

Chemically Defined* (CD)

  • Ingredients have a known chemical structure (defined by a chemical formula). Examples include small molecules, salts, carbohydrates, amino acids, fatty acids, and steroids.
  • Does not contain proteins, hydrolysates, or other ingredients with a complex structure or unknown composition.

Animal Origin-Free* (AOF)

  • Is not manufactured using any raw material ingredients derived from an animal (including human) tissue, cell, or body fluid (i.e. at the primary level of manufacturing); no animal-derived materials are used as a starting material or in the primary level manufacturing process.
  • The components used to manufacture the raw material ingredients are not derived from an animal tissue, cell, or body fluid (i.e. at the secondary level of manufacturing).
  • Ingredients and components may be produced by or extracted from plants, bacteria, or yeast, or cell-free systems derived from them, or may be produced by organic synthesis.
  • May contain recombinant animal or non-animal proteins, provided they are expressed in plants or microorganisms.

Animal Component-Free* (ACF)

  • Does not contain any ingredient that is either an animal (including human) tissue or body fluid or that is isolated or purified from an animal tissue or body fluid.
  • May contain recombinant animal or non-animal proteins, including those produced in animal cell lines or by fermentation processes.
  • Animal-derived components may have been used as raw materials at the secondary or tertiary level of manufacturing, unless otherwise indicated.

Xeno-Free* (XF)

  • Does not contain ingredients derived from non-human animals.
  • Does not contain recombinant materials made from non-human animal DNA sequences.
  • May contain purified, processed, or unprocessed materials from human sources.
  • May contain recombinant materials made from human, plant, bacterial, or yeast DNA sequences.
  • Animal-derived components may have been used as raw materials at the secondary or tertiary level of manufacturing, unless otherwise indicated.

Serum-Free (SF)

  • Does not contain serum, plasma, or hemolymph as an ingredient.
  • May contain ingredients that are processed or derived from blood, serum, or plasma (e.g. albumin, transferrin, low-density lipids, hormones, and platelet lysate).
  • May contain other biological ingredients that are not serum, plasma, or hemolymph (e.g. tissue extracts, such as bovine pituitary extract, platelet lysate, growth factors, hormones, and carrier proteins).

Defining Ingredients and Raw Materials

  • Primary level ingredients: Ingredients directly used to manufacture a finished product. An example of a primary level ingredient would be recombinant insulin included as a component in a cell culture medium.
  • Secondary level of raw materials: Includes starting materials used directly to manufacture a primary level ingredient. An example of a secondary level raw material would be the peptones used in a culture medium to grow E. coli, which then expresses the recombinant insulin used as a primary level ingredient in a cell culture medium.
  • Tertiary level of raw materials: Includes starting materials used directly to manufacture a secondary level component. An example of a tertiary level raw material would be a culture medium to grow yeast for producing peptones that are then used as a component to grow E. coli expressing recombinant insulin, which is directly used as a primary level ingredient in a cell culture medium.

Need Technical Assistance?

STEMCELL Technologies Product and Scientific Support is available to answer your questions and troubleshoot your protocols.

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Assessing the Safety of Culture Media as Ancillary Materials

In the translation from bench to bedside, determining the safety of ancillary materials (AMs; also referred to as raw materials) used to manufacture therapies is critical for clearing the path to the clinic. For culture media in particular, qualification as an AM in cell and gene therapy applications can be challenging due to the lack of a universal system for defining media formulations, leaving researchers and regulators to navigate the multitude of available options and definitions that can vary substantially between suppliers.

One way to assess a culture medium for AM use is through its “viral-safe profile”, which traces the risk of viral exposure from the AM, specifically from its components and subcomponents. Regulators expect traceability through to the subcomponent level, so it is not sufficient to provide evidence of the animal-free nature of an AM’s primary-level components alone. Importantly, supplier claims around animal components in cell culture media are NOT standardized, so it is critical that you work with your supplier to evaluate their claims, such as by obtaining documented evidence through a detailed Certificate of Origin (CoO).

Taking the above approach, you can then “grade” culture media based on the relative ease of verifying their viral safe profile. For example, AOF media has no animal components at all, so it is easy to verify. Although it can be more burdensome to collect evidence of a viral-safe profile for products that contain animal components, it is not impossible to do so, particularly if your supplier works closely with you.

At STEMCELL, we will work with you to provide viral-safe evidence and documentation as available. Importantly, documentation to support the viral-safe profile of our cGMP products—including media containing animal components—is available as a Certificate of Analysis (CoA) and a detailed CoO.

Why Definitions Matter

You can rest assured that when we claim a STEMCELL product is cGMP-compliant, we mean that it is specifically manufactured in compliance to relevant cGMPs, rather than simply in a GMP-compliant facility. Similarly, we hold our media definitions to the strictest standards, so that you can be confident that AOF truly means AOF for all primary- and secondary-level raw materials used.

Related Resources

Qualification of Ancillary/Raw Materials for Clinical Use

Walk through the steps required to qualify ancillary/raw materials for clinical use in this ISCT-hosted webinar with Lynn Csontos, STEMCELL’s Director of Quality Affairs.

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Support for Your Regulatory and Compliance Needs

Get more information about qualifying ancillary materials—including how we can work with you to meet your regulatory requirements—and find definitions to common regulatory terms.

Explore Now >

*Animal-Related Product Information: For products classified as animal component-free (ACF), animal origin-free (AOF), xeno-free (XF), or chemically defined (CD), STEMCELL Technologies verifies that raw materials meet our internal animal origin requirements. STEMCELL relies on supplier-provided documentation for information related to ingredient origin and composition, including the use of animal-derived materials during the manufacturing process. Not all information may be known beyond the ingredient level. STEMCELL’s manufacturing and packaging facilities are multi-use.