@misc{10481/70551,
year = {2021},
month = {6},
url = {http://hdl.handle.net/10481/70551},
abstract = {A range of biopharmaceutical products are used to target Vascular Endothelial Growth Factor (VEGF), including Eylea (R) (aflibercept, AFL) and Zaltrap (R) (ziv-aflibercept, ziv-AFL). The first is indicated for ophthalmological diseases such as neovascular (wet) age-related macular degeneration, while the second is used in the treatment of metastatic colorectal cancer. The stability of AFL in prefilled syringes has been widely studied; however, no research has yet been done on the stability of ziv-AFL in polyolefin infusion bags. Therefore, the purpose of the present research is to evaluate the stability of ziv-AFL (Zaltrap (R)) clinical solutions prepared under aseptic conditions in polyolefin infusion bags at two different concentrations, i.e. 4.0 and 0.6 mg/mL, and stored refrigerated in darkness at 2-8 degrees C for 14 days. With that aim, the ziv-AFL clinical solutions were assessed by analysing changes in its physicochemical and functional properties. The distribution of the particulates was studied over a range of 0.001-10 mu m by Dynamic Light Scattering (DLS); oligomers were analysed by Size-Exclusion High-Performance Chromatography with Diode Array Detection (SE/HLPC-DAD); the secondary structure of the protein was studied by far UV Circular Dichroism (CD) and the tertiary structure by Intrinsic Tryptophan Fluorescence (IT-F) and Intrinsic Protein Fluorescence (IP-F); charge variants were assessed by Strong Cation Exchange Ultra High-Performance Chromatography with UV detection (SCX/UHPLC-UV); functionality was evaluated by ELISA by measuring the biological activity as manifested in the extension of the immunological reaction of the ziv-AFL with its antigen (VEGF). Neither aggregation nor oligomerization were detected by the techniques mentioned above. Secondary and tertiary structures remained unchanged over the 14-day period, as did charge variants. The functionality observed initially was maintained along time. Therefore, it could be proposed that the ziv-AFL clinical solutions studied showed great physicochemical and functional stability over a period of two weeks, regardless of the concentration, i.e. 4 or 0.6 mg/mL.},
organization = {Project FIS (Instituto Carlos III, Ministerio de Economia y Competitividad, Spain)	PI-17/00547},
organization = {European Commission},
publisher = {Elsevier},
keywords = {Ziv-Aflibercept},
keywords = {Fc-fusion protein},
keywords = {Infusion bags},
keywords = {Stability study},
title = {Stability study over time of clinical solutions of ziv-aflibercept prepared in infusion bags using a proper combination of physicochemical and functional strategies},
doi = {10.1016/j.jpba.2021.114209},
author = {Hermosilla, Jesús and Pérez Robles, Raquel and Salmerón García, Antonio and Casares Atienza, Salvador and Cabeza, José and Navas Iglesias, Natalia Africa},
}