Development and Validation of Analytical Methods to Determine the Prolonged in-use Stability of Anticancer Monoclonal Antibodies in Clinical Practice

Abstract

Background/purpose: Personalized dosing of monoclonal antibodies (mAbs) based on body weight and surface area may result in leftovers that need to be discarded due to the absence of stability data. After manufacturing, these mAbs undergo extensive quality control with a panel of methods. With some of these similar methods, these mAbs could be tested to see if stability is maintained after the opening of the pharmaceutical product vial and dilution for administration in a daily clinical setting. Prolonged in-use stability may reduce unnecessary waste and minimize the financial loss of these expensive drugs.Methods: Previously, based on extensive literature research, a complementary panel of methods was selected including visual inspection colour, apparency and, clarity (CAC), size exclusion chromatography (SEC), enzyme-linked immunosorbent assay (ELISA), dynamic light scattering (DLS), thermal denaturation (Tm), and aggregation (Tagg) determination, pH and dye ingress method. We evaluated, developed, and validated these methods with respect to the accuracy, precision, reproducibility, stability-indicating capability, carry-over, limit of quantification (LOQ) and limit of detection (LOD) for nivolumab and pembrolizumab as prototype anticancer mAbs.Results: Analytical results show that stability can be determined