How Reproducible Is Feraheme® (Ferumoxytol Injection)? Comparison of Size, Zeta Potential, and Complement Activation of Different Batches over 15 Years

Abstract

Ferumoxytol injection, also known as Feraheme®, is an approved IV injectable iron supplement and an experimental MRI contrast agent. Initially, it was approved as an IV bolus agent, but its use was later limited to a slow infusion drip due to high levels of infusion reactions. We collected various batches of ferumoxytol with expiration dates ranging from 2010 to 2025 and compared their size and zeta potential. Since nanoparticle surface properties can affect infusion reactions, we conducted a dot blot immunoassay to measure complement C3 opsonization with ferumoxytol preparations. We observed differences in nanoparticle size and zeta potential between batches and a 2.5-fold variation in complement activation. Interestingly, older batches from 2010 showed more uniform size distribution and lower complement activation than some of the newer batches. This finding may be valuable to the nanomedicine community and regulatory authorities.