Chapter 8 – Stem Cells and Cell Therapy: Autologous Cell Manufacturing

Cell therapy is being considered for, or has already shown to aid in, the repair of multiple tissue types in such wide-ranging therapeutic areas as cardiovascular disease, peripheral arterial disease, liver disease, diabetes, neurodegenerative disorders, bone repair, and spinal cord injuries. Two cellular therapies are vying for the emerging cell therapy market: autologous (patient specific) and allogeneic (patient independent). Each approach has potential benefits along with unique challenges, including manufacturing challenges. The cell manufacturing process must meet both Food and Drug Administration regulations and the requirements of a successful business model. In addition to a manufacturing platform, several other regulatory requirements around cell-product characterization must be in place to have a commercially viable cell product. These are outlined in 21 Code of Federal Regulations 610. Overall, the product must be safe, pure, and effective. To provide this level of assurance, full product characterization is necessary, typically using both in vitro and in vivo assays. The applicant must provide evidence of product safety, sterility, purity, identity, and potency (the quantitative measure of biological activity). These measurements are necessary for the approval of all biological products and they must be completed for final product release of each manufacturing lot before administration to the patient. This is a particular challenge in patient-specific therapy, in which a separate release is required for each cell dose. There is a restricted amount of final product, which limits the capability to test the final product. There can also be time constraints because of the potential short shelf life of the product.