Translating a pluripotent stem cell differentiation process from bench to bedside requires a cell culture medium that supports your ambition — in terms of both performance and regulatory requirements.
The use of pluripotent stem cell-derived cells for regenerative medicine has been one of the great promises in the field. However, many researchers are setting up their differentiation protocols at research scale without considering the practical consequences of their reagent and instrument choice for GMP-compliant manufacturing. Here are a few aspects that should be considered early-on to ensure seamless transition to clinical applications:
Choosing a GMP-grade cell culture medium
Having a “GMP” label on your media bottle is not a carte blanche for regulatory approval. With the cell therapy market gaining momentum, an increasing number of companies has been using the word “GMP” as a marketing asset for their reagents. However, there is no mandatory regulation to define what GMP means for a particular ancillary (US) or raw material (EU). This leaves the evaluation of safety and suitability of a particular reagent for GMP-compliant manufacturing processes in the responsibility of the end user. In a situation where suppliers have different standards for their GMP-grade reagents, end users must compare and understand these divergent specifications.
Use of animal components
Recently, more and more cell culture media containing bovine components (e.g. FCS or BSA) have become available with GMP label. This may create the impression that such media are fully equivalent to their xeno-free or chemically defined counterparts when it comes to regulatory approval for the manufacturing of a cell therapy product. However, while additional documentation regarding origin and quality of the animal-component is certainly helpful for risk assessment, it does not eliminate the risk for TSE/BSE transmission in the first place. In a market environment, where animal component-free alternatives exist and have become state-of-the-art, it is questionable whether regulatory bodies will continue to approve BSA- or serum-containing formulations for future clinical trials.
Safety of cytokines and growth factors
In order to ensure the safety of your cell culture media, all its ingredients must support the overall quality claim of the formulation. For instance, in a xeno-free or chemically defined formulation all recombinant growth factors should originate from well-documented expression systems and should avoid the use of FCS or other animal components.
iPSC cultures are complex systems and rely on the interplay of multiple factors such as media, growth factors, and matrices, as well as your favorite cell line and handling routine. Changing parts of the culture system before entering clinical studies is an option. However, that means that equivalence with your current culture system has to be demonstrated, which ends up in the repetition of experiments that had already been completed. Taking the decision for your manufacturing media early on, helps to avoid futile cycles of reevaluation.
Scientific Poster: GMP-compliant expansion of pluripotent stem cells
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