Chimeric Antigen Receptor T-cell Therapy: Production Process Improvement

Abstract

Amid the increasing demand for cancer medications, Chimeric Antigen Receptor (CAR) T-cell therapy plays an important role as an effective treatment despite its high cost. This thesis portrays an assessment of the current state of the CAR T-cell therapy manufacturing process, the development of a reliable demand estimation model for the treatment, and the proposition of an improved state of the production process by introducing a resilient inventory management model along with lean manufacturing principles to the current production process. Pertinent to the current state assessment, a value stream map (VSM) was developed following a comprehensive analysis of the manufacturing process based on previous literature. According to the current state assessment, the "vein-to-vein" time is relatively high, which can lead to complications for patients. Given the increasing demand, it is recommended to reduce the "vein-to-vein" time by improving the production process for CAR T-cell therapy. As a first step toward the improvement, the impact of the health expenditure per capita (HEPC) and the human development index (HDI) on the medication demand was investigated. After finding a strong correlation between the two variables, a ridge regression model was developed using R software to minimize the correlation’s impact. Finally, the impact of at least one variable on the demand was proved using bootstrapping method concluding that the developed ridge regression model is reliable to estimate the demand for cancer medication. After that, a periodic inventory model with an objective to minimize the cost coupled with lean manufacturing principles were introduced to the production process based on the demand estimated using the developed ridge regression model. This practice was reflected by introducing controlled inventory “supermarkets” into two main stages in the production process. This improvement led to a reduction of the total cost by three times, and the “vein-to-vein” time nine by times.