title: A systematic evaluation of mechanisms, material effects, and protein-dependent differences on friction-related protein particle formation in formulation and filling steps.
abstract: Particle formation by physical degradation during the compounding step of biopharmaceuticals is a common concern and found in vessels with bottom mounted stirrers. It was potentially linked to sliding bearings, however, the exact mechanism was still unclear. In this study, custom designed small scale bearings in combination with an IgG1 antibody as model protein were used for investigations of the degradation mechanism inside a bearing. Thereby, abrasion of adsorbed proteins by contact sliding was identified as prevailing protein degradation mechanism and was quantified by an increase in turbidity and by monomer loss. As the protein degradation was highly dependent on combinations of the material of the bearing and the buffer solution, a test system was introduced which allowed to study these effects. Results from the test system using IgG1 and recombinant human growth hormone confirmed a protective effect of Polysorbate 80 by a reduction of protein adsorption, which was strongest in combination with a highly hydrophobic sliding material (PTFE). Finally, a comparison of degradation products from various stresses by ATR-FTIR revealed a high similarity between friction-related degradation products. Therefore, abrasion of adsorbed proteins is very likely the prevailing physical degradation mechanism in processing steps where contact sliding occurs.
authors: Department of Pharmaceutical Development, Sandoz GmbH, Langkampfen, Austria; Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria. Electronic address: lukas.brueckl@sandoz.com.
authors: Lukas
authors: L
authors: Brückl
authors: Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria.
authors: Rainer
authors: R
authors: Hahn
authors: Department of Pharmaceutical Development, Sandoz GmbH, Langkampfen, Austria.
authors: Mauro
authors: M
authors: Sergi
authors: Department of Pharmaceutical Development, Sandoz GmbH, Langkampfen, Austria.
authors: Stefan
authors: S
authors: Scheler
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical / Q000379:methods; D017276:Friction; D019382:Human Growth Hormone / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D007074:Immunoglobulin G; D019382:Human Growth Hormone
keywords: Abrasion; Adsorption; Compounding; IgG antibody; Protein stability; Surfactant