3PC-062 Impact of the preparation of 1.0 mg/mL nivolumab clinical solution on the particulates (aggregation) measured by dynamic light scattering: NaCl and glucose concentration and agitation effect

Background and importanceNivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that binds to programmed death receptor 1 (PD-1) and blocks its interaction with PD-L1 and PD-L2. As a complex protein, routine handling or unintentional mishandling of its solutions may cause degradation that could remain unnoticed but could potentially compromise the clinical safety and efficacy of the drug product.1 Aim and objectivesTo assess the impact on the nivolumab (Opdivo) aggregation process promoted by slight modification in the concentration of the compound (NaCl 0.9% or glucose 5%) used to prepare the clinical diluted solution of nivolumab at 1.0 mg/mL. Also, to assess the impact on the aggregation on nivolumab clinical diluted solutions (1.0 mg/mL, in NaCl 0.9% and glucose 5%) promoted by agitation stress.Material and methodsNivolumab (Opdivo, 10 mg/mL) was diluted at 1 mg/mL using different NaCl (from 0.5% to 1.5%) and glucose (from 1% to 10%) solution concentrations. Also, clinical diluted solutions were subjected to manual gentle agitation (for 30 s and 1 min) and vortex agitation (Vortex VibraMix, 3000 rpm for 10 s, 30 s and 1 min). Particulate was tracked by dynamic light scattering (DLS) using a Malvern Zetasizer Nano ZS90.ResultsReference samples of diluted nivolumab at 1.0 mg/mL in NaCl 0.9% and 5% glucose showed a single particulate population with a hydrodynamic diameter (HD) of 9.66±2.96 nm and 10.67±2.68 nm, respectively, attributed to nivolumab monomers. No significant changes were obtained for HD when the concentration of the diluents was changed. Also, no significant changes were observed after performing the agitation stresses, showing that the HR values were always in the interval of the size of the monomers.Conclusion and relevanceVariation in NaCl and glucose concentrations around the clinical concentrations of 0.9% and 5% did not promote aggregation in a 1 mg/mL nivolumab solution detected by DLS. Also, agitation did not have any impact on aggregation on this clinical nivolumab solution.References and/or acknowledgementsNejadnik MR, et al. J Pharm Sci 2018;107:2013–19.Funded by project FIS: PI-17/00547 (Instituto Carlos III, Spain), which means it was also partially supported by European Regional Development Funds.AT-L is currently receiving an FPU predoctoral grant (reference FPU18/03131) from the Ministry of Universities, Spain.Conflict of interestNo conflict of interest