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 firstname.lastname@example.org.
- 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)
- The finished product contains or used in its manufacturing processes raw materials that have a known chemical structure and concentration (e.g. small molecules, salts, carbohydrates, amino acids, fatty acids, steroids, etc.).
- The product does not contain proteins, hydrolysates, or other raw materials with a complex structure or unknown composition. The finished product does not contain or use in the manufacturing process any raw materials that are derived directly from animal (including human) tissue or body fluid.
Animal Origin-Free* (AOF)
- The finished product does not contain or use in the manufacturing processes any primary and secondary raw materials that are derived directly from animal (including human) tissue or body fluid. The tertiary raw materials may be derived from animal (including human) tissues, body fluid or cell lines.
Animal Component-Free* (ACF)
- The finished product does not contain or use in the manufacturing process any primary raw materials that are derived directly from animal (including human) tissue or body fluid.
- The product may contain recombinant animal proteins, including those produced in animal cell lines or by fermentation processes. Secondary and tertiary raw materials may be derived from animal tissues.
- The finished product does not contain or use in the manufacturing process any primary raw materials that are derived directly from non-human animals or that are recombinant materials made from non-human animal DNA sequences.
- The primary raw materials may be purified, processed or unprocessed materials from human sources or may contain recombinant materials produced in plant, bacterial, or yeast expression systems or in human cell lines. Secondary and tertiary raw materials may be derived from animal components.
- The finished product does not contain any primary raw materials that are serum, plasma or hemolymph but may contain other biological materials (e.g., tissue extracts such as bovine pituitary extract, platelet lysate, growth factors, hormones and carrier proteins).
- The primary raw materials may be processed or derived from blood, serum or plasma, e.g. albumin, transferrin, low-density lipids, hormones and platelet lysate.
Assessing the Safety of Culture Media as Ancillary Materials
In the translation from bench to bedside, determining the safety of ancillary materials (AMs; referred to as raw materials in Europe) 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 the raw materials used to manufacture it and how those raw materials themselves were manufactured. Regulators expect traceability through to the secondary raw material level, so it is not sufficient to provide evidence of the animal-free nature of an AM’s primary-level raw materials 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.
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.
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.
*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.