Viscosity increase/gelation of therapeutic IgG monoclonal antibodies induced by Zn: One possible root cause of clogging of staked-in-needle prefilled syringes.

We investigated the elution of zinc ions (Zn) from the elastomer of rigid needle shields (RNS) attached to staked-in-needle prefilled syringes (SIN-PFS) and the physicochemical impacts of Zn on therapeutic IgG monoclonal antibody (mAb) solutions. The elution of metal ions from typical RNS elastomer under realistic buffer and storage conditions was investigated by inductively coupled plasma-mass spectrometry. Among the metal ions examined, only Zn was detected. The elution of Zn from RNS elastomer was found to be buffer-dependent. We investigated the influence of Zn on the viscosity of seven mAb solutions at 180 mg/mL. The effect of Zn clearly depended on antibody type. Drastic increases in viscosity or gelation were observed in four out of the seven mAbs. Dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) showed the effect of Zn on mAb viscosity was explained by the colloidal destabilization of mAb solutions. Thus, Zn leaching from RNS elastomer may possibly increase viscosity or cause gelation, and consequently cause possible needle clogging during long-term storage. DLS and SAXS can predict reactivity of mAbs to Zn, and require only small amounts of samples. This makes it possible to predict compatibility with RNS elastomer and evaluate needle clogging risk in SIN-PFSs in the early stages of mAb development.