Evaluation of Particle Techniques for the Characterization of Subvisible Particles From Elastomeric Closure Components.

Evaluating a particle profile for parenteral drug products is a well-known challenge due to inevitable variability of results with limited accuracy to actual particle levels present in the product, especially in the subvisible particulate (SbVP) range. It is important to understand the appropriate SbVP counting/characterization technology, methodology capability, and the particle source (intrinsic or extrinsic). Elastomeric closures are prevalent in many types of drug product container closure systems and are a known source of particle contribution. These components need to be considered when establishing a drug product particle profile. In this work, we describe available particle extraction methodology and its applicability in the analysis of elastomeric closure components using multiple detection technologies. Optimum sample preparation and analytical techniques were established to evaluate submicron particle and SbVP loads from elastomeric closure components. In addition, the impact of stopper siliconization and polysorbate 80 interaction on the degree of SbVPs in the final drug product was assessed.