Assessment of Flexible Dosing Volumes in an Existing Spring-Driven Autoinjector Platform

Area of Science:

• Pharmaceutical Engineering
• Drug Delivery Systems
• Biotechnology

Background:

• Autoinjector platforms require dosing volume flexibility for streamlined development and dose adjustments without changing drug concentration.
• Evaluating reduced fill volumes is critical for adaptable drug product development.

Purpose of the Study:

• To present a framework for assessing the performance of spring-actuated autoinjector platforms at fill volumes below their original design.
• To evaluate dose accuracy, injection time, needle dynamics, and drug product quality under low-fill conditions.

Main Methods:

• Utilized a Zwick machine for dose accuracy and injection time evaluation.
• Employed high-speed imaging for needle dynamics analysis.
• Recommended Size Exclusion Chromatography (SEC), Micro-Flow Imaging (MFI), and Hydrophobic Interaction Chromatography (HIAC) for assessing protein aggregation and subvisible particles.
• Included visual inspection for syringe integrity.

Main Results:

• The framework was applied to three autoinjector models (0.5, 1, and 2 mL) with up to 50% fill volume reduction.
• Consistent performance was maintained despite increased driving-rod acceleration and syringe stress.
• Dose accuracy remained comparable to nominal fills; injection time decreased up to 40%.
• Subvisible particles decreased, and no syringe breakage occurred, with low failure probability for AI 3.

Conclusions:

• The standardized framework effectively assesses low-fill autoinjector performance, informing early platform development and design.
• This approach supports flexible dosing strategies and can accelerate regulatory submission timelines.
• It is particularly relevant for large volume autoinjectors designed for variable fill volumes within the same platform.