Prolonged in-use physicochemical and biological stability of nivolumab and pembrolizumab diluted in saline infusion bags and in partially used medication vials.

Abstract

Aim/background: The aim of this study was to determine long-term physicochemical and biological stability of nivolumab and pembrolizumab diluted in saline infusion bags and partially used medication vials. This may enable the prolonged clinical use of these expensive monoclonal antibodies (mAbs) to minimize the economic loss.

Methods: Sterile nivolumab and pembrolizumab concentrates in partially used medication vials and compounded nivolumab and pembrolizumab infusion solutions were stored for two and four weeks, respectively, at 2-8°C in the dark. Subsequently, concentrates and compounded solutions were stored for an additional two weeks under ambient temperature and light conditions. A panel of validated and complementary methods, consisting of enzyme-linked immunosorbent assay, size exclusion chromatography, and dynamic light scattering, were used to assess the biological and physiochemical stability of these mAbs.

Results: All samples showed that purity and concentration had remained within the criteria of <5% as stated in the European Pharmacopoeia. Diluted in infusion bags, nivolumab and pembrolizumab remained biologically and physiochemically stable for up to four weeks when stored at 2-8°C in the dark with an additional two weeks of ambient temperature and light. Stability in partially used medication vials was demonstrated for at least two weeks when stored at 2-8°C in the dark with an additional two weeks of ambient temperature and light.

Conclusion: The findings of this study justify the storage and clinical re-use of sterile nivolumab and pembrolizumab in partially used medication vials and compounded IV infusion bags for up to six weeks. This minimizes the risk of economic loss due to waste. Moreover, these findings support the batch-wise compounding of fixed-dose and dose-banded nivolumab and pembrolizumab infusion bags.