Extended stability of a biosimilar of trastuzumab (CT-P6) after reconstitution in vials, dilution in polyolefin bags and storage at various temperatures

摘要

This study assessed the long-term stability of the trastuzumab biosimilar CT-P6 (Herzuma?, Biogaran) in vials under various storage conditions; after reconstitution of the lyophilized powder (21 mg/mL) and after dilution for final concentrations of 0.8 mg/mL and 2.4 mg/mL in polyolefin bags, stored at 4°C and 22°C.Methods: The physical and chemical stability of the drug was evaluated by several complementary methods.Results: After 90 days of storage at both 4°C and 22°C, no signs of physical instability, such as the formation of aggregates or oligomers, were observed, regardless of the antibody concentration. After 90 days at 4°C, there was no change in the distribution of the seven ionic variants of the compound. The tertiary structure of the compound was unaltered after storage for 28 days at 4°C.Discussion: When stored at 22°C for 28 days, tertiary structure was slightly altered and there were signs of hydrolysis, but no observable aggregate formation or significant signs of thermodynamic destabilization. The same conclusions can be made for reconstituted vials at 21 mg/mL.Conclusion: The trastuzumab biosimilar CT-P6 remained physically and chemically stable for at least 90 days, when stored at 4°C and away from light. These results strongly support the safe use of this biosimilar in several contexts such as preparation in advance, dose banding, supply of prepared but un-administered drug or cold chain rupture. Such usage could improve patient management, lessen nurse and pharmacy workload, and avoid non-justified losses of this expensive drug.