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Establishing scalable technology platforms that allow for varying levels of production throughout the different stages of clinical testing can minimize process development timelines, drug-comparability risks, and - ultimately - costs.
Regenerative therapies based on living cellular products will change the way medicine is practiced and will revolutionize healthcare over the next 10 to 20 years. However, developing commercial products within the context of pharmaceutical regulations is a challenge. Many hurdles can be tackled systematically by understanding future manufacturing requirements and creating focused research-and-development programs. The ultimate goal is to develop scalable processes that maintain the important biological functionalities of this new class of drugs, while controlling the cost of goods (COG) of these inherently expensive products. The field of protein-based molecular therapeutics has driven many areas of significant technological development that can serve as a foundation for innovative large-scale processes whose final product is living, functional cells.
When developing a cell-manufacturing process, it is important to make the product required for the clinical trials using technologies that enable commercially viable lot sizes. Manufacturing at clinical-stage-appropriate scales is critical, as over-engineered processes will generate excess product at a high COG - a sub-optimal way to use scarce cash resources.
When planning for product development and commercial manufacturing, it is necessary to establish both the characteristics of the final product and the expected production volumes (i.e., in number of cells per year). These cell requirements can then be used to create a staged processdevelopment strategy. A staged development plan will allow for appropriate clinical-phase production while minimizing the risk of altering the safety or efficacy of the product as the process is Scaled up. Modeling COGs throughout clinical development will aid in controlling costs once the product is ready to enter the market, as well as highlight where early technology-development spending will yield the best rerum on investment.
This article outlines many of the criteria that need to be evaluated during the clinical development of allogeneic (i.e., universal donor) cell products that require a culture-expansion step. It also highlights some of the common manufacturing platforms for current therapeutic-cell-manufacturing processes. (Other therapeutic-cell-product formats, such as autologous, patient-specific, or non-culture-expanded allogeneic therapies, are beyond the scope of this article.)
Integrated process development - upstream and downstream
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