Extended physicochemical stability of cetuximab in opened vials and infusion bags when stored at 4°C and 25°C

Abstract

Introduction: This study aimed to determine the stability of cetuximab: (1) under "in-use" conditions after dilution to 1 mg/mL in 0.9% sodium chloride in polyolefin bags and (2) as an undiluted solution (5 mg/mL) repackaged in polypropylene bags or kept in the vial after opening.

Methods: Ready-to-use 500 mg/100 mL vials of cetuximab solution were diluted to 1 mg/mL in 100 mL bags of 0.9% sodium chloride or repackaged as a 5 mg/mL solution into empty 100 mL bags. Bags and vials were stored at 4°C for 90 days and 25°C for 3 days. A syringe sample of 7 mL was taken from each bag for the initial determinations. The sampled bags were weighed to determine their initial weight and placed under the planned storage conditions. The physicochemical stability of cetuximab was estimated using validated methods.

Results: No changes in turbidity, no protein loss, and no changes in cetuximab tertiary structure were observed after 30 days of storage or when subjected to a temperature excursion of 3 days at 25°C and when stored at 4°C for up to 90 days, regardless of the concentrations and batches. The colligative parameters did not change under any of the tested conditions. No evidence of microbial growth was found in bags after 90 days of storage at 4°C.

Conclusion: These results support the extended in-use shelf-life of cetuximab vials and bags, which can be cost-effective for healthcare providers.

Keywords: In-use stability; cetuximab; temperature excursion.

Figure 1.

Organization of cetuximab samples.

Figure 2.

Second derivative ultraviolet spectrum of cetuximab diluted to 1 mg/mL or transferred to an empty bag as a 5 mg/mL solution and stored at 4°C.

Figure 3.

Fluorescence emission spectrum of diluted cetuximab stored for 30 days at 4°C.

Figure 4.

Ion chromatography profiles of cetuximab with eight identified peaks indicated (main peak = no. 5).