Analytical comparability to evaluate impact of manufacturing changes of ARX788, an Anti-HER2 ADC in late-stage clinical development

• Published in: PloS one Vol. 18; no. 7; p. e0284198
• Main Authors: Yu, Wayne, Ramprasad, Mysore P, Pal, Manoj, Chen, Chris, Paruchuri, Shashi, Skidmore, Lillian, Knudsen, Nick, Allen, Molly, Buechler, Ying
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.07.2023; Public Library of Science (PLoS)
• Subjects: Amino acids; Antibodies; Antibodies, Monoclonal - chemistry; Antibody-drug conjugates; Antineoplastic Agents; Biological products; Biology and Life Sciences; Breast cancer; Chromatography; Cytotoxicity; Developmental stages; Dosage and administration; Drug dosages; ErbB-2 protein; Immunoconjugates; Ions; Manufacturing; Manufacturing industry; Medicine and Health Sciences; Metastasis; Molecular weight; Monoclonal antibodies; Oligopeptides; Physical Sciences; Potassium; Product quality; Research and Analysis Methods; Viral antibodies; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0284198

ARX788 is an anti-HER2 antibody drug conjugate (ADC) developed using Ambrx proprietary Engineered Precision Biologics technology. The manufacturing process of ARX788 has been optimized during the course of early to late-phase clinical development. A comprehensive evaluation of side-by-side comparability between pre- and post-change process for ARX788 drug substance and drug product from a quality perspective was conducted based on ICH Q5E guidelines consisting of batch release assays, physicochemical and biophysical characterization, biological characterization, and forced degradation studies. All results have substantiated a high degree of similarity between the pre- and post-change ARX788 drug substance batches and drug product lots, demonstrating that the process manufacturing changes did not impact product quality.