Photostability studies on Nivolumab in formulation and in diluted saline and glucose solutions for parenteral infusion

Photostability studies on Nivolumab in formulation and in diluted saline and glucose solutions for parenteral infusion Benedetta Fongaro, Valentina Cian, Patrizia Polverino de Laureto and Giorgia Miolo Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Italy We investigated the impact of some stress factors, i.e., shaking, vibrations and light exposure on Nivolumab, a fully human immunoglobulin G4 anti-PD-1 monoclonal antibody approved for multiple advanced tumours, including melanoma [1], trying to mimic the real life of this protein drug once it has been released from the pharma industry and shipped to the hospital pharmacy. A critical exogenous stressing factor is indoor and outdoor light exposure to which a drug product could be exposed during transport but particularly within the hospital and during the hours of administration to the patient [2]. Chromatographic, electrophoretic, and spectrophotometric analyses were performed on the intact product and after dilution in sterile saline and glucose solutions to compare the structure of Nivolumab before and after the stressor steps. Nivolumab demonstrated a general instability to light and particularly in the diluted glucose solution, suggesting the role of glucose degradation products in the formation of aggregates and photooxidation products of the mAb. In conclusion, upon exposure to light, this product may undergo a change in structure, chemistry and likely functional properties that could have a potential impact on the safety and efficacy of this very active mAb in the anticancer therapy. [1] Caroline Robert, et al. (2015). Nivolumab in Previously Untreated Melanoma without BRAF Mutation. N Engl J Med, 372, 320-330