Cetuximab stored in vials, bags for days remains stable

A recent study has demonstrated the extended physicochemical stability of cetuximab in opened vials and infusion bags, which can help save costs for healthcare providers.

“Cetuximab may be stored in vials (500 mg) for 30 days after opening and for 30 days after diluting in 0.9% sodium chloride (NaCl) to a concentration of 1 mg/mL or transferring into an empty bag,” the researchers said. “Cetuximab may also be stored for 90 days at 4 °C without any noteworthy physical or chemical changes.” [J Oncol Pharm Pract 2024;doi:10.1177/10781552231170583]

The thermal cycling study further shows that storage of samples for 3 days at 25 °C does not compromise the integrity of cetuximab. “Cetuximab stored in this manner has sufficient stability to accommodate storage problems, such as interruption of the cold chain for 48 to 72 h,” according to the researchers.

To determine the stability of the study drug, ready-to-use 500 mg/100 mL vials of cetuximab solution were diluted to 1 mg/mL in 100 mL bags of 0.9% NaCl or repackaged as a 5-mg/mL solution into 100 mL bags. These vials and bags were stored at 4 °C and 25 °C for 90 and 3 days, respectively.

For the initial determinations of stability, the researchers took a syringe sample of 7 mL from each bag. They then weighed the sampled bags to find out the initial weight and placed these under the planned storage conditions. Validated methods were used to estimate the physicochemical stability of cetuximab.

Results showed no protein loss, no changes in turbidity and in cetuximab tertiary structure after 30 days of storage or when subjected to a temperature of 25 °C for 3 days and when stored at 4 °C for up to 90 days, regardless of the concentrations and batches.

There was also no change seen in colligative parameters under any of the tested conditions. In addition, microbial growth was not found in bags after 90 days of storage at 4 °C.

Ionic variants

Eight cetuximab isoforms or variants were identified, similar to the findings of an earlier study by Farjami and colleagues. [N Engl J Med 2012;366:321-329]

“Ion chromatography did not reveal any change in distribution of ionic variants, signifying the absence of modification of the initial structure, especially deamidation,” the researchers said. “Derivative ultraviolet and fluorescence spectral analysis did not reveal any changes in the tertiary structure of the antibody during storage at 4 °C for 90 days or after 3 days of thermal excursion at 25 °C.”

Identical thermal denaturation curves were also observed, which indicate the absence of thermodynamic destabilization of the entire three-dimensional structure. Matchings results were seen for the vials after opening.

“Although cetuximab has been shown to be sensitive to mechanical stresses such as stirring, no sign of aggregation was observed in this study,” the researchers said. “This finding demonstrates that typical handling procedures, such as dilution, bag filling, or withdrawing by syringes, do not alter the extended stability of cetuximab.” [Ann Pharm Fr 2009;67:340-352]