Antibody-Drug Conjugate Manufacturing: Facility Design, Process Safety, and Regulatory Considerations.

This paper presents an in-depth examination of the manufacturing, formulation, and fill/finish processes for traditional antibody-drug conjugates (ADCs), with particular emphasis on cytotoxic ADCs and the unique risks associated with their production. ADCs inherent toxicity demands rigorous facility and equipment design, proactive risk assessment, and robust risk mitigation strategies. We describe the multiple processes and facility types involved in producing ADCs, with a more detailed focus on drug product facilities. In addition, we study the critical facility risk areas encountered and effective strategies for managing and overcoming those risks. While it is well understood that containment is a critical risk area in the ADC modality, there has been a significant amount of work published with respect to specific containment strategies and solutions for unique unit operations and this area has only been summarized in this review. The paper also addresses regulatory compliance-highlighting EU GMP Annex 1 expectations-and underscores the importance of robust containment strategies and holistic design elements for preventing cross contamination, personnel exposure, and mitigating environmental impact.