Multiphysics Simulation of Needle Clogging in Pre-Filled Syringes.

Needle clogging in prefilled syringes can impede drug product injection and negatively impact drug product quality. Computer simulations provide a useful tool to understand clogging mechanisms and elucidate design strategies to minimize or avoid clogging. In this talk, we present multiphysics simulations of clogging in needle syringes prefilled with a monoclonal antibody solution. We use these simulations to evaluate several putative clogging mechanisms, including: (1) fluid ingress into the needle and subsequent solvent evaporation leading to a dried solid plug, and (2) shear-induced jamming driven by rapid plunger compression. We study the impact of solution properties, needle diameter, barrel hub shape, and plunger speed on the onset of clogging. The effect of protein concentration on the solution viscosity is considered. Simulations such as these can offer insight into the critical material, geometric, and operational parameters that increase the probability of clogging, as well as a method to systematically triage drug product formulations based on their clogging probability. Based on these insights, we illustrate how simulations can be leveraged to effectively design prefilled syringes to minimize clogging probabilities for a given drug product formulation.