Development of media production processes for CAR-T therapies

Many of the standard cell culturing unit operations utilized by early stage CAR-T manufacturing processes have been derived from benchtop scale academic processes and require further development to become commercially viable. Critical unit operations, such as isolation, activation, transduction, and expansion are often the focus of next generation or automation technologies. Development of ancillary processes such as medium production, however, should not be overlooked and can take advantage of economies of scale and technologies that have been proven in other pharmaceutical industries like biologics. Special consideration should be taken when developing these medium scale-up processes since cell therapies are complex and can be highly sensitive to medium composition changes. In addition, significant changes may be needed to update medium production processes from a process suited for an academic setting to one suited for a commercialized product. This poster discusses Celgene’s approach for developing a commercially sustainable media preparation process by applying available filtration and bulk solution preparation technologies and the unique challenges associated with applying these technologies to CAR-T therapies

CAR T manufacturing: process modifications for a transformational autologous product on a rapid path to licensure

The transformational impact of CAR T cell therapies on serious diseases demands a rapid path to licensure in order to establish widespread availability to desperate patients. In addition, the complex, labor intensive, and costly patient-specific manufacturing processes for CAR T cell therapies demand process modifications that enable scalability and affordability to maximize availability to patients. There are many options to improve CAR T processes ranging from automation to improved medium composition to simplified closed-system tubing sets. However, the dramatic dose-dependent safety and efficacy activities of these therapies amplifies the need for maintaining product comparability across process changes. This assessment of comparability is challenged by limited knowledge of product Critical Quality Attributes as well as limited availability of patient cells for process development studies. We have developed a comprehensive analytical toolbox that enables the assessment of product impact of process changes along with a risk-based approach to applying a matrix of appropriate tools for each change. This risk-based approach involves the most extensive product analysis for high-risk changes and a relatively restricted product analysis for low-risk changes. In all cases, the product analysis includes assessments of product characteristics that can hypothetically be impacted by the process change. We describe our approach to identifying, prioritizing, and assessing feasibility of process changes along with generating a suitable product comparability dataset to implement the most impactful process changes on an expedited timeline to licensure. We share examples of comparability data and its application to decision making