While a number of characterization methods are available for analyzing subvisible particle content in protein pharmaceuticals, counting and characterizing particles within the entire subvisible size range remains a challenge due to the properties of the particles themselves and to limitations of the instrumentation.  Methods relying on differences in refractive indices of the particle and solution (e.g. light obscuration, flow microscopy, etc.) are limited for small particle sizes (< 2 um) while methods for characterizing smaller aggregates (e.g. SEC, DLS, FFF, AUC, etc.) are not able to count individual particles.  Additionally, silicone oil droplets contribute to subvisible particle counts for samples stored in prefilled syringes, which are increasingly being used for biotherapeutic products.     Here, we evaluate a method that relies on differences in particle buoyant mass for characterization of particles in the range of ca 0.5 � 5 um.  A model particle system was specifically designed to evaluate the suspended microchannel resonator (SMR)'s ability to distinguish between buoyant particles (e.g. silicone oil) and dense particles (e.g. protein particles).  In addition, this emerging technique was applied to high concentration monoclonal antibody solutions stored in prefilled syringes in stressed stability studies.  It is shown that the SMR system can potentially distinguish between silicone oil droplets and protein particles in a size range that is challenging for many subvisible particle characterization methods.

Exploring Archimedes' principle to distinguish subvisible protein particles from silicone oil in the 0.5 um to 5 um range

243rd National Meeting (2012)

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