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TCH-026 Long-Term Study of the Formation of Aggregates in Undiluted Cetuximab 5 mg/ml
  1. A Martínez-Ortega1,
  2. A Salmerón-García2,
  3. N Navas-Iglesias1,
  4. J Hernández-Jiménez1,
  5. J Cabeza-Barrera3,
  6. LF Capitán-Vallvey1
  1. 1University of Granada, Analytical Chemistry, Granada, Spain
  2. 2Baza Hospital, Hospital Pharmacy Unit, Baza, Spain
  3. 3University Hospital San Cecilio, Hospital Pharmacy Unit, Granada, Spain

Abstract

Background Cetuximab (Erbitux) is a chimeric monoclonal IgG1 antibody, an epidermal growth factor receptor (EGFR) inhibitor, given by intravenous infusion for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is produced in a mammalian cell line (Sp2/0) by recombinant DNA technology.

Purpose To evaluate the stability of this therapeutic monoclonal antibody, i.e. cetuximab 5 mg/ml in solution for infusion, in terms of the formation of aggregates once the vial was open. The study was carried out for up to 15 days since the manufacturer only indicates chemical and physical in-use stability for up to 48 hours at 25ºC, if the solution was prepared in validated aseptic conditions.

Materials and Methods The study of the formation of the aggregates was carried out by using a size exclusion high performance liquid chromatography method with a diode array detection method (SE-HPLC-DAD. Two different storage conditions, i.e. refrigerated at 4°C and frozen at −20°C, were considered up to 15 days. Samples were characterised by chromatographic analysis immediately after the vial was opened. These chromatographic data were compared with those obtained on subsequent days. A stress study was also conducted.

Results Analysis of freshly-prepared samples enabled us to characterise cetuximab chromatographically by SE-HPLC-DAD. In the corresponding chromatograms monomers were clearly detected (peak at 6.77 ± 0.05 minutes of retention time) while dimers or aggregates (peaks at retention times near to 6 minutes or smaller) were absent. Chromatographic analysis of the same samples stored at room temperature and protected from light in a refrigerator at 4°C and frozen at −20°C over a 15-day period indicate the absence of any kind of aggregates.

Conclusions The results of this study indicated the absence of the aggregate formation in cetuximab 5 mg/ml during the period of monitoring (15 days) under the two storage conditions tested.

Acknowledgment This work was supported by funds received by the Project PI10/00201 (Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion, Spain). We also thank the Pharmacy Unit of the University Hospital San Cecilio which kindly supplied all the cetuximab samples studied.

No conflict of interest.

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