Stability study of Durvalumab solutions in its opened vials and after dilution and storage in 0.9% NaCl infusion polyolefin bags

Background
Durvalumab is a humanized immunoglobulin G1-kappa monoclonal antibody indicated as monotherapy for the treatment of adult patients with non-small cell lung cancer. Currently, according to the summary of product characteristics (SmPCs) the product is stable in solution for 24 hours at +4°C and for 12 hours at room temperature. However, this stability period is generally based on a microbiological risk, which is controlled in Controlled Atmosphere Zones (CAZs) in which Durvalumab solutions are handled.

Objectives
Evaluation of the potential changes in the stability of Imfinzi® leftovers (50mg/ml) and diluted Durvalumab (1mg/ml and 5mg/ml) in 0.9% polyolefin NaCl bags.

Material and Methods
The bags and vials were stored for 3 weeks at 4°C, then at room temperature (25°C) for a 3 days-period (temperature excursion). The physico-chemical stability was evaluated by different methods such as dynamic light scattering, steric exclusion chromatography (SEC) and ion chromatography, as well as analysis of pH, osmolality, turbidimetry and protein determination by UV spectrophotometry. Structural stability of the antibody was also evaluated: the analysis of the primary structure was performed by peptide mapping, the secondary structure by infrared (IR) spectroscopy and the tertiary structure by UV spectrometry and fluorescence. Analyses were performed in triplicate. All methods used were validated and demonstrated as stability indicators for the antibodies.

Results
After 3 weeks of storage at 4°C (including 3 days at 25°C), no signs of physical instability were observed, which means there was no submicronic and micronic aggregate and particle formation. The SEC chromatographic profiles showed no change in monomer ratios over time and no oligomer or fragment formation. Ion chromatography showed no significant change in the distribution of ionic variants, indicating the absence of modification of the initial structure, including deamidations. Finally, no structural modification of the antibody was observed during the study.

Conclusion
All of these results show that Durvalumab remained stable for at least 3 weeks at +4°C. In addition, a 3-day temperature excursion at 25°C does not appear to alter the antibody’s stability. However, the study was performed on a single batch of Durvalumab. Therefore, additional data are required to complete this study, especially working on 3 different batches.