(M1530-11-61) Evaluating Zeta Potential's Role in Monoclonal Antibody Manufacturing and Medical Application

Purpose: Monoclonal antibodies (mAbs) are crucial in therapeutic and diagnostic applications due to their specificity and high affinity for antigens. However, their stability, efficacy, and interaction with various surfaces during manufacturing and application can be significantly influenced by their physicochemical properties, including zeta potential. This study aims to delineate the critical role of zeta potential measurements in optimizing the stability and efficacy of monoclonal antibodies (mAbs) throughout their manufacturing and medical applications. We specifically explore how electrostatic properties influence mAb interactions with manufacturing surfaces and medical device materials, impacting therapeutic effectiveness.

Methods: Our research employed two primary analytical approaches. The first utilized the Litesizer DLS 500 for dynamic, static, and electrophoretic light scattering to assess monoclonal antibody characteristics, focusing on zeta potential, particle size and molecular mass determination. The second approach utilized the SurPASS 3 electrokinetic analyzer to investigate monoclonal antibody adsorption on silicone medical tubing, analyzing changes in zeta potential under various conditions, such as pH adjustments and surfactant interactions. These methods provided comprehensive insights into the physicochemical properties and interaction behaviors of mAbs.

Results: Determination of the particle size distribution and molecular mass of mAbs are crucial parameters to determine purity and conformational integrity of the product. Zeta potential measurements and determination of the isoelectric point with the Litesizer DLS 500 revealed the sensitivity of mAbs to environmental factors and their adsorption tendencies, essential for maintaining quality during manufacturing and application processes. The SurPASS 3 analyses demonstrated that modifications in zeta potential significantly influenced mAb adsorption on medical tubing, highlighting a decrease in protein loss through targeted surface modifications of tubing materials.

Conclusion: The study underscores the pivotal role of zeta potential in the development and application of monoclonal antibodies. Understanding and managing electrostatic interactions through precise analytical measurements allow for enhancements in the stability and efficacy of mAbs, thereby optimizing therapeutic outcomes and mitigating issues related to protein adsorption on biomedical surfaces.

Zeta potential measurements as a function of pH, performed on the monoclonal antibody sample (5 mg/mL) using the Litesizer coupled to the Dosing System.

Effect of surfactant concentration on the mAb adsorption by using a 2.5 mM KCl solution at pH 5.4.

Adsorption and desorption kinetics of mAb on the inner surface of the silicone tubing measured by the dynamic streaming potential method in 2.5 mM KCl at (A) pH 5.4, (B) pH 7.4, (C) pH 9.0 at constant pressure (Δp = 200 mbar) and constant volume flow rate. D: Adsorption of non-ionic surfactant PS 20 (0.004%) prior to the adsorption of mAb at pH 5.4.