Evaluation of the sterility, stability, and efficacy of bevacizumab stored in multiple-dose vials for 6 months.

PURPOSE

The aim of this study was to determine the sterility, stability, and efficacy of a commercially available brand of bevacizumab for 6 months of being stored in multidose vials at 4 degrees C.

METHODS

Bevacizumab was aseptically and repeatedly drawn four to five times from new vials into syringes for clinical use within the first month; the remaining bevacizumab was left in the vials and refrigerated at 4 degrees C for 0, 1, 3, and 6 months for research. Each time before bevacizumab was withdrawn and every weekend when it was not sampled, the rubber top of each vial was disinfected by using 10% povidone-iodine solution and an isopropyl alcohol wipe. Each vial had been sampled for less than 12 times during the experimental periods. All vials were analyzed for microbial growth. The stability of bevacizumab was analyzed by MALDI-TOF MS (matrix-assisted laser desorption ionization/time-of-flight mass spectrometry). The efficacy of bevacizumab was analyzed by enzyme-linked immunosorbent assay (ELISA). At each time period, bevacizumab was mixed with vascular endothelial growth factor (VEGF)-165 and left undisturbed for 3 h. The efficacy of bevacizumab was then evaluated by measuring the concentration of residual-free VEGF-165.

RESULTS

No microbial growth was obtained from any of the bevacizumab samples during each time period, indicating that the bevacizumab stored at 4 degrees C after the vials had been pierced remained sterile. MALDI-TOF MS analysis revealed that the 1-, 3-, and 6-month samples were stable, and there were no molecular-weight changes among any of the samples. The level of degradation of bevacizumab at 1, 3, and 6 months was compared with that of the control (0 months). The results of ELISA showed less than 10% degradation at all time periods.

CONCLUSIONS

This study suggests that if aseptic precautions are followed while using bevacizumab, the contents of multiple-dose vials stored at 4 degrees C will remain sterile. The anti-VEGF activity of bevacizumab stored at 4 degrees C will remain stable for up to 6 months.