Tungsten residues in prefilled syringes promote monoclonal antibody aggregation and charge heterogeneity

Monoclonal antibodies (mAbs) are pivotal therapeutics; however, their stability during production and storage remains a critical challenge, particularly in prefilled syringes (PFS), where tungsten residues from manufacturing can compromise quality. This study systematically evaluates the effect of tungsten-derived from syringe needle pin extracts and commercial tungsten salts (sodium tungstate, sodium metatungstate)-on the stability of three therapeutic mAbs under accelerated conditions (40 °C, light). Using a multi-analytical approach (size-exclusion chromatography (SEC), capillary electrophoresis-sodium dodecyl sulfate (CE-SDS), light obscuration (LO), and ion exchange chromatography (IEC)), we demonstrate that tungsten pin extracts induce markedly more aggregation, fragmentation, and subvisible particle (SbVP) formation than commercial salts (a 14-fold increase in aggregates for mAb-2 at 100 ppm), with concomitant light further worsening these outcomes. We demonstrate, for the first time, that tungsten-driven degradation induced destabilization to colloidal instability (reduced T_agg) without affecting conformational stability (T_m), and is mediated by deamidation-induced acidic variants. Computational modeling suggests that mAb-2's heightened sensitivity might correlate with solvent-exposed asparagine residues. Collectively, our data highlight the imperative for tight tungsten control during PFS manufacture and antibody-specific stability assessments to mitigate risks to product quality.