In recent years, ADC has been at the forefront of cancer therapy due to their target specificity. An ADC consists of 3 main components: an antibody attached to a linker system which is used to attach one or more individual molecules of a small cytotoxic agent to the antibody. To date, there are 13 ADCs approved by the United States food and drug administration (FDA) for the treatment of hematological and solid organ cancers. Though all FDA-approved ADCs are developed in lyophilized form, there is a lack of mechanistic understanding of the solid-state stability of ADCs from the literature. The formulation development of ADCs is similar to that of proteins or antibodies but with more complicities with the addition of payload and linkers. The hydrophobic payloads affect overall ADC stability to a great extent, especially depending on the drug to antibody ratio (DAR) values. The hydrophobic components of ADC molecules create entropically unfavorable states while in contact with water. Thus, ADC are at higher risk of aggregation in an aqueous environment. 300 Furthermore, the linker stability also plays an essential role in ADCs stability in the context of a process, in vivo systemic circulation and product storage. The stability of ADCs is questionable if formulated in solution due to the risk factors associated with the linker system, particularly hydrazone linkers may undergo in vitro cleavage and release the cytotoxic drug during storage. Lyophilization may lower the degradation rates by lowering the mobility of molecules. Most of the stability evaluation of lyophilized formulation focuses on the in vivo activity of ADCs. Rowland et al. found lyophilized idarubicin antibody conjugate retained bioactivity for more than 100 days during storage at -20℃. 298 Jaime et al. found that lyophilized paclitaxel-antibody conjugate with trehalose as sugar stabilizer demonstrated the best pharmacological activity, whereas PEG alone or a combination of PEG and trehalose resulted in compromised immunological and cytotoxic activities. Barbour et al. studied the stability of lyophilized BR96doxorubicin conjugate and found the acid-catalyzed hydrazone hydrolysis induced major degradation in solution formulation. This study demonstrated improved long-term solid stability in the presence of lactose or sucrose after lyophilization using size exclusion chromatography (SEC). A recent report has also demonstrated the correlation between ADC storage stability and protein structure and matrix interaction characterized by ssHDX-MS under accelerated conditions. Although there is growing interest in developing liquid formulations based on the increased knowledge and experience with ADCs and the improved physicochemical properties of the new generation of ADCs, few such feasibility studies have been reported in the literature to date. It is desired to maintain payload attachment to antibodies over prolonged durations in solution. This emerging trend places significant emphasis on the design of linkers and payloads, conjugation methods, properties of the parent antibodies, as well as formulation and device development, all of which are crucial for preventing payload detachment.