Commercialization of Cell Therapies: A CDMO Perspective.

Cell and gene therapies (CGT) hold tremendous curative potential for the treatment of devastating diseases, such as Parkinson's disease, Type I diabetes, and various types of cancer. Besides demonstrating the safety and efficacy of these therapies, it is important to address several challenges in early development and clinical manufacturing to commercialize cell and gene therapies and meet the demand to treat many patients. The source and intensity of challenges can vary as these therapies move from early clinical to late-stage clinical and commercialization readiness. Here, we highlight some of the main challenges the CGT industry faces from the contract development and manufacturing organization (CDMO) perspective and some of the bioprocessing best practices required to de-risk these challenges in the path to commercial launch.The key to commercializing cell and gene therapies is to establish a step-by-step, phase-appropriate, risk-assessment-based approach to meet the product lifecycle requirements from early development to clinical and late-stage commercial readiness campaigns. In this journey, it would be critical to cover key aspects of chemistry, manufacturing, and controls (CMC), including materials, manufacturing process, analytics, sterility assurance, equipment, and technology, as well as tissue acquisition, depending on the type of application. Appropriate process improvement studies may be needed, including implementing innovative technologies with proper in-process control and monitoring analytical methods to ensure the robustness and reproducibility of the manufacturing process. In particular, it may be necessary to eliminate open and variable manual unit operations while incorporating comprehensive characterization assays to verify the long-term stability of the products. Implementing an automated, scalable, computer-controlled 3D bioreactor in the process, with appropriate downstream and cell-processing technologies, would be critical to minimizing commercialization risks and producing high-quality cell therapy products. Finally, in preparation for commercial launch, the commercialization readiness campaign should be based on a Failure Mode and Effects Analysis (FMEA) to identify modes of failure, risks, and mitigations and design appropriate process characterization studies prior to process validation.