In Part I of our series on “New Strategies Key to the Clinical Manufacturing of Stem Cells for Therapeutic Use” we will look at ways to optimize stem cell culture media for clinical manufacturing. For the most part, stem cell culture media still contains serum or animal derived products to maintain healthy cell processes. The use of any animal product can be problematic due to the inherent inconsistency of products derived from animals. Primary challenges include sourcing difficulties, high batch-to-batch variation, and safety concerns involving infectious agents. As a result there is considerable discussion in the industry around clinical stem cell manufacturing and whether regulatory bodies including the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) will put restrictions on the use of animal products in stem cell therapeutics. As a result, the stem cell culture community is routinely examining new ways to remove or reduce serum and other animal derived media components.

In addition to production problems, the use of animal products raises many safety issues around possible contamination. The Food and Drug Administration (FDA) and other regulatory bodies discourage use of these animal components because of safety concerns involving the risk of viral and prion (the infectious causative agent associated with Mad Cow Disease) contamination. The FDA recently published a guidance that would require a warning label be added to all products containing plasma-derived albumin in their manufacture. The warning would state that due to the plasma-derived source of the albumin, the albumin may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease and the Creutzfeldt-Jakob disease agent. Please see our recent blog “FDA Issues Guidance for Warning Labels on All Drugs Produced Using Blood Products Including Plasma-Derived Albumin,” for more information. The warning label, impacts any product that includes plasma-derived albumin either in the finished product or during manufacturing. This applies to several vaccines and recombinant therapeutics on the market and would also apply to stem cell products that are approved for therapeutic use.

Whether regulatory bodies eventually make it mandatory or not, animal-free stem cell culture should be the goal. In addition to removing safety concerns, it removes product quality and inconsistency issues that are common with animal products. Consistent raw material quality is crucial to safe, reliable manufacturing. One challenge is that many stem cell lines do not grow well without the addition of serum or animal derived products such as plasma-derived albumin and transferrin.

The good news is that now there are many companies working on animal-free alternatives. These products are defined, animal-free and allow for the reduction or removal of serum and animal products from culture. Today companies including Sigma, Fisher Scientific, InVitria, Sheffield Bioscience, and Mediatech offer cell culture supplements that can be used as alternatives to animal components. These products include recombinant human albumin and recombinant human transferrin both of which have been successfully used in stem cell applications to replace their animal-derived counterparts. The availability of human recombinant versions of these proteins also allows the formulation of xeno-free stem cell media. Other companies including Vitro Biopharma, TNCBio, Lonza, and Stem Cell Technologies manufacture animal-component free media. Please see the table below for a list of media supplements for stem cell culture.

The advantage of these new products is that they eliminate the problems associated with serum, like inconsistency, possible contamination and sourcing challenges, without compromising cell health and productivity. They also aid in the transition from animal containing to animal-free media. The development of new media solutions that are not only serum free, but also animal component free will lead to scalable and commercially viable clinical manufacturing of stem cell therapies.

Has anyone used these products in their stem cell culture? Does anyone have a success story to share involving serum-free stem cell culture?

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