Background and Importance Cetuximab (CTX) is a monoclonal antibody indicated for treatment of metastatic colorectal cancer and squamous cell cancer of head and neck. These kinds of proteins are susceptible to degrade during long-term storage and/or during exposure to environmental conditions (high temperature, agitation, light exposure, etc) when handled in hospitals. Therefore, it is essential to detect critical degradation points before the administration to patients to ensure the efficacy and safety of the medicine.

Aim and Objectives To assess the impact of accelerated light (stress) and natural sunlight exposures on CTX (Erbitux^®, 5 mg/mL) safety and efficacy through the study of aggregation formation and functionality when mishandling in real hospital conditions.

Material and Methods CTX (Erbitux^®, 5 mg/mL) fresh opened vials were used to carry out the study. Light stress was performed in an accelerated stress test chamber to simulate sunlight (250 W/m², 24h, 25°C), while another sample of CTX was exposed to natural sunlight for 24h. Aggregate formation was evaluated by Size-Exclusion Ultra-High-Performance Liquid Chromatography (SE/UHPLC-UV) and functionality was assessed by Enzyme-Linked Immunosorbent Assay (ELISA).

Results SE/UHPLC-UV chromatograms of CTX control sample (5 mg/mL) showed a main chromatographic peak assigned to CTX monomers. The sample subjected to light stress revealed the appearance of three new chromatographic peaks assigned to high molecular weight species (HMWS). However, exposure to natural sunlight only revealed the appearance of one small new peak assigned to HMWS with a low relative abundance. ELISA showed a significant loss of functionality of CTX medicine in both stressful conditions: light stressed sample revealed a loss of biological activity (BA) of around 20%, while the sample exposed to natural sunlight showed a loss of BA of 10%.

Conclusion and Relevance Exposure to light promotes aggregate formation in CTX (Erbitux^®), this effect being more noticeable in accelerated light exposure. Moreover, CTX functionality was also affected after the exposure to both stressful conditions, revealing a loss of biological activity. Thus, we recommend preventing CTX from light exposure when handled in hospitals.

References and/or Acknowledgements Funded by project FIS PI17–0547 Instituto Carlos III, Ministerio de Economía y Competitividad (Spain), also supported by European Regional Development Funds (ERDF). A.T-L grants a FPU predoctoral contract (FPU18/03131, Ministry of Universities, Spain).

Conflict of Interest No conflict of interest.