Biological stability of Durvalumab solutions in its opened vials or after dilution and storage in 0.9% NaCl infusion polyolefin bags

Objective
Durvalumab is an anti-PDL1 human IgG1 kappa monoclonal antibody used for the treatment of adult lung cancer. According to the supplier’s recommendations, the stability of Durvalumab in solution were initially 24h at 4°C and 12h at room temperature (RT). This stability has recently been extended to 30 days at +4°C and 24 hours at RT. We demonstrated by convergent methods that the physicochemical stability of Durvalumab in diluted solution at 1 mg/ml and 6 mg/ml or concentrated (50 mg/ml vials after opening) was maintained for at least 4 weeks at 4°C. Furthermore, we also demonstrated that these diluted solutions could be stored 7 days at 25°C (protected from light) without physicochemical alterations. The purpose of this work is to assess the biological stability of Durvalumab solutions diluted at 1 and 6 mg/ml and vials at 50 mg/ml after opening.

Methods
Solutions of Durvalumab were diluted in 0.9% NaCl at concentrations of 1 and 6 mg/ml and packaged in infusion polyolefin bags. These bags were prepared sequentially and stored at 4°C or 25°C to carry out all the biological tests on the same day for all the samples. Physicochemical analyzes (ion and size exclusion chromatography, dynamic light scattering, UV and fluorescence spectroscopy) were performed to ensure the compliance of these solutions.
Inter-batch variability had been analyzed during the physicochemical stability study, the tests were therefore carried out using the same batch of Durvalumab and in triplicate. The biological stability of the samples was evaluated on one hand using a commercial ELISA test which measures the quantity of Durvalumab present in the bag and on the other hand by flow cytometry which detects the binding of the antibody to the cell surface. The PDL1-expressing MDA-MB231 cell line grown in vitro was used for flow cytometry assays using a polyclonal secondary antibody specific for human IgG. The samples stored at 4°C were studied on D0, D14 and D28. The samples stored at 25°C on D0 and D7.

Results
Compared with the functional activity at D0, no significant difference was observed between the different samples at the different concentrations and storage conditions studied. Durvalumab’s ability to bind to its target is stable at 4°C for 28 days and 7 days at room temperature at 1 mg/ml and 6 mg/ml. The same is true for Durvalumab at 50mg/ml in a vial after opening.

Discussion-Conclusion
The biological stability of Durvalumab indicates that the binding of Durvalumab to PDL1-expressing cells is not altered under the conditions evaluated here. These results suggest that the mechanisms involved in the clinical effect are conserved and therefore add more stability data on Durvalumab. The stability of preparations made in anticancer production unit could therefore be reconsidered.

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