Sustained Anti-Vascular Endothelial Growth Factor Activity of Aflibercept (Eylea) After Storage in Polycarbonate Syringes Used for Intravitreal Injection: A Pathway to Safety and Efficiency

J Ocul Pharmacol Ther. 2019 Jun;35(5):278-282. doi: 10.1089/jop.2018.0085. Epub 2019 Mar 27.

Abstract

Purpose: Aflibercept (Eylea™, Regeneron) is supplied in single-use glass vials along with 1 cc polycarbonate syringes. We sought to determine if storage of aflibercept for sustained periods within these syringes would result in loss of antivascular endothelial growth factor (anti-VEGF) activity. Methods: Aflibercept samples were drawn from commercially available glass vials into manufacturer-supplied 1-mL syringes and stored at 4°C. Anti-VEGF activity was assessed using enzyme-linked immunosorbent assays at the following storage durations: 0, 4, 9, 14, and 28 days. Frozen samples stored at -20°C for 28 and 56 days were also assayed. Also, a subset of aflibercept samples was stored and then diluted to 1:10 and progressively smaller concentrations and the assays repeated. Aggregation of aflibercept was tested using a dynamic light scattering assay. Results: There were no statistical differences in anti-VEGF activity among aflibercept samples of 1:1 or 1:10 dilution stored at either 4°C or -20°C at any of the storage intervals (P > 0.05). We also observed persistence of robust anti-VEGF activity for up to 14 days when diluted poststorage to 1:16,000, a concentration that would be expected after >7 vitreous half-lives within the eye (estimated at >50 days). No evidence of drug aggregation in specimens stored for 14 days was observed. Conclusions: Our findings support feasibility of prefilling and storage of aflibercept within manufacturer-supplied polycarbonate syringes for as long as 14 days before use under pharmacy-based sterile conditions, facilitating greater safety and efficiency in many clinics delivering anti-VEGF therapy.

Keywords: aflibercept; anti-VEGF activity; safety; storage; syringe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Drug Storage
  • Humans
  • Intravitreal Injections
  • Polycarboxylate Cement / chemistry*
  • Receptors, Vascular Endothelial Growth Factor / chemistry
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacology*
  • Vascular Endothelial Growth Factors / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Polycarboxylate Cement
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factors
  • aflibercept
  • polycarbonate
  • Receptors, Vascular Endothelial Growth Factor