Wen Lili, Zhang Yuanyuan, Sun Chenxi, Wang Shawn Shouye, Gong Yuhui, Jia Chunyuan, Luo Jianjun
Department of Bioconjugate Product Development and Manufacturing, WuXi XDC Co., Ltd., Wuxi, Jiangsu, P.R. China.
Business Enablement North America, XDC ConjuTech USA LLC, Middletown, DE, United States.
Antib Ther. 2025 Mar 9;8(2):99-110. doi: 10.1093/abt/tbaf005. eCollection 2025 Apr.
Antibody-drug conjugates (ADCs) have emerged as a rapidly expanding class of therapeutics driven by their superior specificity and clinical efficacy. 14 out of 16 commercially approved ADCs are formulated as lyophilized forms because ADC is generally considered to be less stable than unmodified antibody. The formulation development for ADCs, particularly liquid formulation, presents unique challenges due to their intricate structural complexity, physicochemical properties, and degradation pathways. This review provides the first comprehensive analysis of formulation strategies employed in commercial ADCs. Furthermore, this review discusses the key areas of focus for ADCs throughout the formulation development workflow, spanning from the initial formulation development to the final stage of drug product manufacturing. In addition, we identify and analyze the distinctive technical challenges in ADC formulation development compared to unconjugated antibody, while proposing potential solutions to these challenges. Finally, we offer strategic perspectives on future directions in ADC formulation development to advance this promising therapeutic modality.
抗体药物偶联物（ADCs）因其卓越的特异性和临床疗效，已成为一类迅速发展的治疗药物。16种商业批准的ADC中有14种制成冻干剂型，因为ADC通常被认为比未修饰的抗体稳定性差。由于ADC结构复杂、物理化学性质独特以及降解途径复杂，其制剂开发，尤其是液体制剂开发面临着独特的挑战。本文首次对商业ADC中采用的制剂策略进行了全面分析。此外，本文还讨论了ADC在整个制剂开发工作流程中的关键关注领域，从最初的制剂开发到药品生产的最后阶段。此外，我们识别并分析了与未偶联抗体相比，ADC制剂开发中独特的技术挑战，同时提出了应对这些挑战的潜在解决方案。最后，我们对ADC制剂开发的未来方向提供了战略展望，以推动这一有前景的治疗方式的发展。
