Quantification, Microbial Contamination, Physico-chemical Stability of Repackaged Bevacizumab Stored Under Different Conditions

Abstract

In this work, the stability of Bevacizumab (Avastin(®)) repackaged in individual 1 mL single-use syringes and stored at different conditions was assessed. Bevacizumab repackaged in single-use syringes results from the off-label use of the drug as an intravitreal agent in the treatment of retinal diseases. Bevacizumab stability was assessed by assaying the anti-VEGF activity using an indirect ELISA method and a Dynamic Light Scattering study. The thermal stability of the drug was also studied by calorimetric analysis, aimed to evaluate thermodynamic parameters associated to the thermal unfolding process. Furthermore, microbiological and fungal tests on the Bevacizumab syringes were performed. As a result, a significant decrease of the anti-VEGF activity was detected when syringes were exposed to UV light at a temperature of 37°C. Under these conditions, the Dynamic Light Scattering study showed an increase of the average size of Bevacizumab; probably due to aggregation. In conclusion, Bevacizumab stability, when stored under different conditions, was assessed considering three different aspects: anti-VEGF activity, microbial contamination and physico-chemical properties. Bevacizumab was found to be stable, under sterile conditions, for 3 months at 4°C and for 7 days at room temperature, exposed to indirect light sources, while a brief exposure of the drug to direct UV radiation proved detrimental to drug stability.

Ziv-aflibercept in macular disease

“…Yannuzzi et al 19 performed a prospective in vitro study of syringes containing intravitreal preparations of bevacizumab from several compounding pharmacies in the USA. Similar findings were previously reported in pharmacies in France, 20 Italy 21 and the UK. 22 There were no microbial contaminants or endotoxin detected in any of the samples.…”

Pharmaceutical compounding of aflibercept in prefilled syringes does not affect structural integrity, stability or VEGF and Fc binding properties

“…We chose four weeks storage duration to address how aflibercept was affected over time and to facilitate comparison with previous studies where the same timeframe has been used 20 – 24 , 26 – 28 . In a Norwegian context one week is the more relevant storage time, as this is the maximum shelf life allowed in Norway when an aseptic production procedure without renewed sterilization is employed.…”

Assessment of bevacizumab quality and stability in repackaged syringes for clinical use

“…In the case of repackaged syringes, the initial and final particle sizes were the same as in the vials, but from day 3 on, double size distribution increased towards far larger sizes with each further storage day. Other authors have detected a double size distribution at different storage conditions and even in control samples 30 34…”

“…Additionally, the new packaging conditions may affect the stability of BEV as a function of storage time33 and thereby compromise its effectiveness 29. Signorello et al 34 have recently determined that storage of repackaged syringes at 37°C under UV radiation, even for short periods of time, leads to BEV degradation.…”