A Quality By Design Approach of Developing a Human Pluripotent Stem Cell Derived Cell Therapy Product.

Advancements in understanding human developmental biology have greatly facilitated the differentiation of diverse functional cell types from human pluripotent stem cells (hPSCs). As a result, over a hundred clinical studies have been initiated, with several cell therapy products progressing to late-stage clinical development. However, ensuring the safety, efficacy, and quality of these cellular therapies remains a significant challenge. This chapter presents a Quality by Design (QbD)-based product development strategy, using a PSC-derived mesenchymal stromal cell-like (MSC-like) therapy as a case study. Given the complex biological nature of these "living" therapeutic agents and the limited prior knowledge available, the approach aligns with ICH guidelines to define the Quality Target Product Profile (QTPP) and applies risk assessment tools, such as risk ranking and filtering, to identify Critical Quality Attributes (CQAs). Additionally, Critical Process Parameters (CPPs) are optimized to enhance manufacturing robustness, addressing challenges related to viability, purity, and aseptic processing. The study also highlights the importance of analytical method validation, raw material control, and lifecycle management in meeting regulatory standards. By integrating QbD principles into PSC-derived therapy development, this work provides a structured framework for producing high-quality cell therapy products and establishes a valuable precedent for future cell-based therapies.