A systematic evaluation of mechanisms, material effects, and protein-dependent differences on friction-related protein particle formation in formulation and filling steps.

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.