Therapeutic protein products used for the differentiation and characterization of subvisible particulates

Introduction

The formation of protein aggregates is a particular concern for parenteral administration biopharmaceuticals due to the potential for increased immunogenicity. As a consequence, there is an expectation from regulatory agencies for companies to monitor and, if required, reduce the levels of sub-visible particles present in therapeutic protein from manufacture through their complete shelf life. While immunogenicity can be induced by a variety of mechanisms, contamination by non-protein material is known to be a potential cause. The presence of silicone oil in parenterals has attracted considerable interest, due to its use in syringe-based administration systems and the difficulty in distinguishing oil droplets from protein aggregates. In addition to protein aggregates, non-biological contaminants may act as nucleation points for aggregate growth. Consequently, particle sizing alone is not sufficient.