Impact of tubing material on stability and filling accuracy of biologic drug product

Abstract

This article is presenting completely new observations linked to Polysorbate 80 (PS80) oxidation in biologics drug product. Indeed, we observed that, in the drug product exposed to long contact time (∼ 1 h) in platinum-cured silicon tubing during the filling, the oxidation of PS80 is dramatically accelerated compared to short contact time. The phenomenon was observed in presence of iron traces (20 ppb), but not in absence of iron (< 2 ppb) or in presence of a chelator like EDTA. Electron Paramagnetic Resonance (EPR) measurements demonstrated the presence of radicals formed during the oxidation. It was deduced that platinum-cured silicon tubing is leaching some radical initiators, most probably peroxides decomposed by the iron. Alternative filling sets made of ThermoPlastic Elastomer (TPE) were investigated, both for the impact on PS80 stability and the filling performance using a peristaltic pump. The results showed that these filling sets were indeed not causing accelerated PS80 degradation but the process was not robust enough; these filling sets being too rigid for the constraints of the peristaltic pump rollers. These results show that there is no practical tubing alternative to platinum silicone cured tubing. To avoid the impact on PS80 oxidation the potential remediations presented in the article are to avoid any trace of iron or to add a chelating agent, or to discard the vials having experimented a filling stop (> 5 min).