The materials and methods used in the biopreservation of source material, intermediate derivatives, and finished cell therapy products greatly influence several critical success factors for final product development and commercialization.
The Cost Per Delivered Dose of a cell therapy product (arguably the most important metric once safety and efficacy are proven) is driven by a yield-cost relationship throughout the biopreservation system. Relationship components include the cost, yield, and stability of source material, as well as the concentration, volume, potency, toxicity, and stability of the finished product.
Stability (in particular) limits the geographic distribution and, hence, revenue potential for the product.
When you optimize the biopreservation system, you positively effect downstream-processing operations and yield-cost relationship.
Biopreservation system optimization may be viewed as a matrix (above). Three key cell/tissue materials comprise the X-axis. The critical success factors (shelf life/stability, true post-preservation recovery and functional yield, and acquisition/processing costs) comprise the Y-axis.
System tuning should focus on enabling the longest stability, maximum functional yield, and lowest cost for each biologic type.
The blue shaded area between the yield and cost lines (above) represents the optimization potential for the system, with the upper-left corner representing the maximum optimized state.
Another critical success factor for a cell therapy product is the geographic distribution potential.
Logistics around the transportation of (1) source and intermediate material from origin to processing facility, and (2) finished product from processing facility to clinical markets, are greatly impacted by stability of the material.
The image above depicts source material/finished product from the US and Europe with potential distribution constrained by poor stability. The red dashed circles represent potential limitations on intercontinental movement of source material and/or distribution of a finished product.
Specific biopreservation system optimization initiatives may include the evaluation of various commercial hypothermic storage and cryopreservation media products in comparison to in-house formulated cocktails.
Particular attention should be paid to the true preservation efficacy of the products. This can be measured in split-sample comparisons.
- Use extended cell stability assays capable of accurately indicating post-preservation viability and functional recovery.
- In the assay, measure the duration of cell stability of the biologic enabled by the biopreservation media.
- Also, compare the quality and regulatory footprint of the biopreservation media products vs. in-house formulations for robustness.
- Evaluate the quality of components (USP grade or multi-compendial, serum-free, protein-free), cGMP manufacturing, FDA/regulatory agency familiarity (i.e., Master File, technical file).
- Select a robust set of release criteria (sterility, endotoxin, and cell-based assays) to evaluate when selecting or changing biopreservation media used in cell therapy product development and commercialization.
Figure 3 illustrates the 72-hour cell stability footprint of human fibroblasts enabled by three commercial hypothermic storage media. Fluorescent staining for cytoskeletal integrity, mitochondrial activation, and cell nuclei is clearly visible in the micrographs.
Clearly, your best biopreservation economics will be realized via utilization of best-in-class biopreservation media because the media has a flow-through effect and impact on the yield-cost relationship.
The ability of optimized biopreservation media products to highly leverage source material and finished product cost, yield, and stability, impacts final product distribution and profit potential.