Background <p>Lyophilization is a strategy widely adopted in the pharmaceutical industry to improve the stability and long-term storage of labile drugs, particularly biopharmaceuticals. Optimization of the lyophilization cycle requires a comprehensive understanding of the lyophilization process and the establishment of an appropriate design space, which has been investigated using various techniques.</p> Area covered <p>This review explores the fundamental principles of the lyophilization process in detail, including freezing, primary drying, and secondary drying, with an emphasis on how each stage influences the properties of drug products. In particular, this review focuses on supporting lyophilization cycle development by evaluating various methodologies, including process analytical technology (PAT), to determine the drying endpoint. Additionally, a systematic approach for constructing a design space to optimize the freeze-drying process and guide an efficient scale-up strategy is presented.</p> Expert opinion <p>Establishing a lyophilization cycle based on scientific principles is crucial for developing robust drug products while ensuring both performance and quality. Real-time process monitoring can be achieved by utilizing various analytical methods such as PAT, enabling the establishment of a robust process that consistently manufactures pharmaceuticals of suitable quality. The optimization of the lyophilization process, supported by the construction of a design space using various models and the scale-up strategy, is anticipated to contribute to the development of robust drug products with improved stability, particularly for biopharmaceuticals.</p>