Stability of intravenous antibody dilutions in clinical use: Differences across patient populations with varying body weights.

Abstract

Antibody-drug conjugate (ADC) plays a crucial role in the treatment of various diseases and intravenous injection is the primary administration route for ADCs due to its high bioavailability. However, this method requires drug preparation and dilution, which can compromise the stability of the solution and increase the risk of aggregation as excipient concentrations are reduced during dilution. Antibody drug dosing is often based on patient body weight and typically diluted in either 0.9% (w/v) sodium chloride or 5% (w/v) dextrose injections. Variations in patient body weight lead to differences in the final concentrations of both the drug and excipients, affecting stability. In this study, we examined the stability of intravenous dilutions for patients with varying body weights using trastuzumab and ado-trastuzumab emtansine ADCs. Analytical techniques including size-exclusion chromatography (SEC), fluid imaging microscopy (FIM), bicinchoninic acid (BCA) assay, and turbidity testing were employed to assess monomer, oligomer, and aggregate levels before and after dilution. Machine learning was applied to distinguish the morphology of sub-visible particles. Our findings reveal that weight-based dosing leads to significant stability differences in intravenous preparations. This study offers important insights into the formulation stability of biopharmaceuticals and their clinical use.