Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration.
The physical and chemical integrity of a biopharmaceutical must be maintained not only during long-term storage but also during administration. Specifically for the intravenous (i.v.) delivery of a protein drug, loss of stability can occur when the protein formulation is compounded with i.v. bag diluents, thus modifying the original composition of the drug product. Here we present the challenges associated with the delivery of a low-dose, highly potent monoclonal antibody (mAb) via the i.v. route. Through parallel in-use stability studies and conventional formulation development, a drug product was developed in which adsorptive losses and critical oxidative degradation pathways were effectively controlled. This development approach enabled the i.v. administration of clinical doses in the range of 0.1 to 0.5 mg total protein, while ensuring liquid drug product storage stability under refrigerated conditions.
['Morar-Mitrica|Sorina|S|', 'Puri|Manasi|M|', 'Beumer Sassi|Alexandra|A|', 'Fuller|Joshua|J|', 'Hu|Ping|P|', 'Crotts|George|G|', 'Nesta|Douglas|D|']
D061605:Administration, Intravenous D000818:Animals D061067:Antibodies, Monoclonal, Humanized D016466:CHO Cells D006224:Cricetinae D003412:Cricetulus D004339:Drug Compounding D004355:Drug Stability D006801:Humans D007074:Immunoglobulin G D055550:Protein Stability
intravenous administration biopharmaceutical stability monoclonal antibody adsorption oxidation CD3, cluster of differentiation 3 CMC, critical micelle concentration Cys, cysteine DSC, differential scanning calorimetry EDTA, edetate disodium Glut, glutathione HPLC, high performance liquid chromatography M, methionine residues MS, mass spectrometry MTG, monothioglycerol Met, methionine PES, polyethersulfone PO, polyolefin PS80, polysorbate 80 PVC, polyvinylchloride SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis antioxidant cIEF, capillary isoelectric focusing dilution i.v., intravenous infusion low concentration low dose mAb, monoclonal antibody surfactant