A new method for pharmaceutical compounding and storage of anti-VEGF biologics for intravitreal use in silicone oil-free prefilled plastic syringes

• Published in: Scientific reports 2019-12, Vol.9 (1), p.18021-10, Article 18021
• Main Authors: Lode, Heidrun Elisabeth, Gjølberg, Torleif Tollefsrud, Foss, Stian, Sivertsen, Magne Sand, Brustugun, Jørgen, Andersson, Yvonne, Jørstad, Øystein Kalsnes, Moe, Morten Carstens, Andersen, Jan Terje
• Format: Article
• Language: English
• Subjects: 631/45/612; 692/700/565; 82; 82/1; 82/103; 82/16; 82/29; Age; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - chemistry; Bevacizumab; Biological products; Biological Products - administration & dosage; Biological Products - chemistry; Chemistry, Pharmaceutical; Diabetes mellitus; Diabetic Retinopathy - drug therapy; Drug Compounding - methods; Drug Stability; Drug Storage - methods; Edema; Humanities and Social Sciences; Humans; Intravitreal Injections; Macular degeneration; Macular Degeneration - drug therapy; Macular Edema - drug therapy; Monoclonal antibodies; multidisciplinary; Oil; Oxidation-Reduction; Plastics; Retina; Science; Science (multidisciplinary); Silicone Oils - chemistry; Silicones; Syringes; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-54226-7

Intravitreal injections of antibody-based biologics targeting vascular endothelial growth factor (VEGF) are highly effective and have markedly decreased the risk of visual impairment associated with prevalent retinal diseases, such as neovascular age-related macular degeneration and diabetes macular oedema. The diseases are chronic in their nature, and most patients need long-term therapy to suppress disease activity. We previously reported a compounding method for repackaging and storage of aflibercept (Eylea), a commonly used anti-VEGF biologic, in silicone oil-coated plastic syringes without compromising drug stability or activity. In addition to improving safety and time spent per patient, compounding of anti-VEGF biologics enables single-dose vials to be split into multiple syringes, thereby considerably reducing waste and drug expenses. However, symptomatic silicone oil droplets may deposit in the eye’s vitreous body after repetitive injections. To fully avoid this complication, we here report on a novel pharmaceutical compounding method using silicone oil-free syringes and a 33 G × 9 mm Low Dead Space Needle hub injection needle. We evaluate the method for three anti-VEGF biologics commonly used in ophthalmology: aflibercept, ranibizumab (Lucentis) and bevacizumab (Avastin). Our results show that compounding and storage for one week does not compromise the functional activity of the biologics and allows for safe and cost-effective compounding of anti-VEGF biologics for intravitreal injections in prefilled silicone oil-free syringes.