Abstract
Purpose :
To study the stability of SYL1801 (a new chemical entity based on RNA interference technology) preservative-free formulation as eye drops to be supplied in multidose containers for prolonged use.
SYL1801 is a siRNA developed by Sylentis to treat patients with neovascular AMD. Currently the compound is running a Phase 2 clinical trial in Europe (NCT05637255). The investigational new drug has been formulated as a preservative-free solution in phosphate buffer saline at physiological pH and isotonicity.
Methods :
Novelia® eye dropper was selected as the primary pharmaceutical packaging in order to study the stability of SYL1801 formulation. Novelia® is a registered trademark of Nemera la Verpillière SAS. This container closure system is able to guarantee sterility without antimicrobial preservatives. This presentation has been tested under ICH stability conditions with two objectives:
- In-Use stability testing to assess the shelf life and storage conditions of SYL1801 formulation in Novelia® after first opening. At least 45-day stability at room temperature after opening were required to support phase 2 clinical trial.
- Long term (1 year) testing under ICH stability conditions and comparison with the same formulation in single unit dose glass vials.
Eye droppers were placed in qualified chambers at the following ICH conditions: 5(±3) °C; 30(±2) °C/35(±5%) RH and 40(±2) °C /NMT 25% RH. Glass vials were placed at 5(±3) °C; 25(±2) °C /60% (±5%)RH; and 40(±2) °C/75% RH. All samples were analyzed at different time-points. Physicochemical and sterility tests were performed to assess that the product is within specifications.
Results :
All formulations showed good stability at the studied conditions and time points.
Conclusions :
SYL1801 investigational new drug shows good stability properties both during in-use and long-term ICH studies. SYL1801 is able to be packed in either in glass vials or eye- droppers being compliant with the specifications that guarantee the integrity of the medication. No differences were observed after 12 months of storage under long-term and accelerated conditions in any of the studied containers. Novelia® container closure system is able to maintain parameters (sterility and physic-chemical parameters) both under standard use conditions and under severe misuse conditions.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.