Khalili H, Sharma G, Froome A, Khaw P T, Brocchini S
1] NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK [2] UCL School of Pharmacy, London, UK.
Moorfields Pharmaceuticals, Moorfields Eye Hospital, London, UK.
Eye (Lond). 2015 Jun;29(6):820-7. doi: 10.1038/eye.2015.28. Epub 2015 Mar 27.
To compare and examine the storage stability of compounded bevacizumab in polycarbonate (PC) and polypropylene (PP) syringes over a 6-month period. PC syringes have been used in a recent clinical study and bevacizumab stability has not been reported for this type of syringe.
Repackaged bevacizumab was obtained from Moorfields Pharmaceuticals in PC and PP syringes. Bevacizumab from the stored syringes was analysed at monthly time points for a 6-month period and compared with bevacizumab from a freshly opened vial at each time point. SDS-PAGE electrophoresis and size-exclusion chromatography (SEC) was used to observe aggregation and degradation. Dynamic light scattering (DLS) provided information about the hydrodynamic size and particle size distribution of bevacizumab in solution. VEGF binding and the active concentration of bevacizumab was determined by surface plasmon resonance (SPR) using Biacore.
SDS-PAGE and SEC analysis did not show any changes in the presence of higher molecular weight species (HMWS) or degradation products in PC and PP syringes from T0 to T6 compared with bevacizumab sampled from a freshly opened vial. The hydrodynamic diameter of bevacizumab in the PC syringe after 6 months of storage was not significantly different to bevacizumab taken from a freshly opened vial. Using SPR, the VEGF binding activity of bevacizumab in the PC syringe was comparable to bevacizumab taken from a freshly opened vial.
No significant difference over a 6-month period was observed in the quality of bevacizumab repackaged into prefilled polycarbonate and polypropylene syringes when compared with bevacizumab that is supplied from the vial.
比较并检测在6个月期间，贝伐单抗在聚碳酸酯（PC）注射器和聚丙烯（PP）注射器中的储存稳定性。近期一项临床研究中使用了PC注射器，但尚未报道过该类型注射器中贝伐单抗的稳定性情况。
从摩尔菲尔兹制药公司获取重新包装在PC和PP注射器中的贝伐单抗。在6个月期间，每月对储存注射器中的贝伐单抗进行分析，并在每个时间点与新开封小瓶中的贝伐单抗进行比较。采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）和尺寸排阻色谱法（SEC）观察聚集和降解情况。动态光散射（DLS）提供了溶液中贝伐单抗的流体动力学尺寸和粒径分布信息。使用Biacore通过表面等离子体共振（SPR）测定血管内皮生长因子（VEGF）结合情况和贝伐单抗的活性浓度。
与从新开封小瓶中抽取的贝伐单抗相比，SDS-PAGE和SEC分析未显示从T0到T6期间PC和PP注射器中存在更高分子量物质（HMWS）或降解产物有任何变化。储存6个月后，PC注射器中贝伐单抗的流体动力学直径与从新开封小瓶中抽取的贝伐单抗相比无显著差异。使用SPR，PC注射器中贝伐单抗的VEGF结合活性与从新开封小瓶中抽取的贝伐单抗相当。
与从小瓶中供应的贝伐单抗相比，重新包装在预填充聚碳酸酯和聚丙烯注射器中的贝伐单抗在6个月期间质量无显著差异。
