Abstract
Purpose :
A dose ranging study is an essential step in early drug development to determine its therapeutic window. The clinical trial requires controlled administration of different dose levels to observe the dose-response profile of a drug. For intraocular applications, dose levels are currently achieved with different concentrations of the same active ingredient in a fixed volume. This cost intensive approach using multiple formulations is taken due to injection volume limitations, and poor accuracy and precision of conventional currently available syringes. An accurate and precise microliter dose injection platform would allow a cost-effective approach to control dose levels by varying volumes of a single formulation concentration.
Methods :
The MDS technical performance was evaluated at two time points, as manufactured (t=0) and after two years (t=24 months) (accelerated aging). At t=0, in vitro delivered dose volumes for four dose levels— 9µL, 25µL, 37.5µL, and 50µL—were measured using a validated gravimetric test method (n=9 each). A bracketing approach was employed for t=24 months; delivered dose volumes were measured for the 9µL and 50µL dose levels. Subvisible particle count and endotoxin content were also both measured at t=0 and t=24 months. The MDS was further tested for biocompatibility.
Results :
The MDS had mean delivered volumes and standard deviations of 9.3±0.5µL, 25.9±0.5µL, 38.0±0.5µL, and 50.2±0.7µL for t=0. And at t=24 months, the 9µL and 50µL dose levels had 8.6±0.2µL and 50.3±0.8µL. Delivered volumes never exceeded the target ±3µL from the intended dose. Subvisible particle count and endotoxin content were within acceptable limits for ophthalmic applications at both time points. The MDS also conformed to all standard test requirements for biocompatibility.
Conclusions :
The results report the MDS as accurate and precise for microliter dosing. Use of the MDS in a human dose ranging clinical trial allowed for dose levels to be clearly controlled with different volumes of a single formulation, where inaccuracies of conventional delivery methods would have clouded results. This resulted in savings from reduced drug and quality control costs. Reliable results were further ensured by the material stability and biocompatibility of the MDS.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.