Design and implementation of a GMP production of a highly potent therapeutic antibody product in a new facility designed for single-use systems

Pharmaceutical biotechnology has significantly advanced with the development of antibody-based therapeutics, revolutionizing treatments for cancer, autoimmune diseases, and infections. This thesis focuses on the design, implementation, and GMP-compliant validation of a new biomanufacturing facility by Philogen S.p.A. in Rosia, Italy, dedicated to producing potent therapeutic antibodies using single-use technologies. The facility adheres to updated EudraLex Volume 4 Annex I guidelines, emphasizing contamination control, process segregation, and real-time monitoring. Antibodies, particularly engineered formats like bispecific antibodies and immunocytokines, present unique manufacturing challenges due to their complexity and lower production yields. The facility is divided into Pre-Viral Inactivation and Post-Viral Inactivation zones to minimize contamination risks. The upstream process utilizes disposable bioreactors for CHO cell line fermentation, while the downstream process includes chromatographic purification and viral clearance. Real-time monitoring ensures process robustness and product consistency. Utilities like Water for Injection and compressed gases are meticulously controlled. Aseptic fill and finish operations are performed under Grade A conditions using single-use systems. Scale-down modeling optimizes process parameters and validation strategies, enhancing efficiency and reducing waste. The facility's qualification follows GMP validation pathways, ensuring compliance with regulatory standards. This thesis provides a blueprint for modern GMP-compliant facilities, integrating advanced technologies to produce next-generation antibody therapeutics safely and effectively.