Reactive impurities in large and small molecule pharmaceutical excipients – A review

Abstract

Reactive impurities in excipients can cause drug product degradation or protein modification even at trace levels, and thus impact drug stability and quality. It is critical to understand the potential impact of these impurities during development in order to ensure a robust clinical and commercial product. In this article, we review reactive impurities in pharmaceutical and biopharmaceutical excipients for both small molecule and large molecule drugs. The common reactive impurities in excipients, including peroxides, aldehydes, organic acids, reducing sugars and elemental impurities are reviewed. Sources of these impurities, reactions and impact, analytical methods, and control and risk mitigation strategies are also discussed.