Physicochemical stability of pembrolizumab admixture solution in normal saline intravenous infusion bag

Pembrolizumab is an anti-PD-1 monoclonal antibody, approved and under development for numerous indications in oncology. It is available as either lyophilized powder for reconstitution or ready-to-use solution. Both are required to be diluted in saline or dextrose solution prior to intravenous infusion. After dilution, the recommendation per summary of product characteristics is 24 h at 2-8℃ and 6 h at room temperature. The purpose of this study was to investigate the physicochemical stability of pembrolizumab diluted solution (1 mg/mL) at both refrigerated and room temperature conditions for an extended period.

Under aseptic conditions, pembrolizumab was diluted in 250 mL of saline injection in polyolefin bags to obtain the final protein concentration of 1 mg/mL. Thus, prepared bags were then stored at either 5℃ ± 3℃, refrigerator exposing the product to ambient light or room temperature (20℃ ± 3℃) on the benchtop.

Using several analytical methods, it was demonstrated that pembrolizumab solution for infusion, diluted in normal saline can be stored in polyolefin infusion bags for at least 1 week at 5℃ or RT with no evidence of chemical or physical instability. No aggregation was observed.

Thus, the practical use of aseptically prepared diluted pembrolizumab in saline can be safely extended to optimize the workload of centralized preparation units and to minimize costs. However, it is the responsibility of the end-user to maintain overall quality of prepared admixture solution that is administered to patient, by following aseptic compounding process as recommended in the packaging insert.