Antibody-Drug Conjugates Drug Product Formulation and Process Development, Scalability and Stability Considerations.

Antibody-drug conjugates (ADCs) combine the target specificity of monoclonal antibodies with the potency of cytotoxic small molecules, offering enhanced therapeutic potential. However, their inherent structural complexity, arising from the interplay of antibody, linker, and payload, introduces unique challenges for drug product (DP) development, stability, and scalability requiring tailored approaches to maintain the quality target product profile throughout the product lifecycle. This review summarizes key formulation and process development considerations for ADCs, with an emphasis on aspects that are particularly distinctive for ADC drug products. Critical degradation risks, such as photo- and heat-induced degradation, are discussed in the context of formulation screening, formulation excipients and primary packaging selection, and DP process design. Basic considerations on analytical tools used to identify and monitor critical quality attributes are provided. Lyophilization strategies, essential for the stability of commercialized ADCs, are recommended using Design of Experiments and modeling approaches. Furthermore, robust DP process control strategies during scale-up are reviewed with a focus on lyophilization, the application of Quality by Design (QbD) principles, and risk-based methodologies to address ADC‑specific challenges. Finally, the review explores the transition from early development to late-phase clinical and commercial stages, underscoring the need for evolving control strategies. Overall, it provides an overview of current practices and challenges in ADC formulation and DP process development, offering strategies to navigate these complexities based on literature and insights from approved ADCs.