Stability studies for biologics

Abstract

Biological products represent a growing segment of the pharmaceutical industry. Stability studies of these complex biologics present challenges beyond those found for the typical small-molecule pharmaceutical. Biologic products are typically only marginally stable, not entirely understood, may demonstrate non-Arrhenius behavior, degrade by multiple pathways and possibly different pathways during different stages of shelf life. Further, subtle changes brought on by stresses can have large effects on the therapeutic properties of the product. There are analytical methodology challenges pertaining to monitoring stability as well, in particular the higher variance and complexity of the product and methodology. The issues and strategies involved in studying the stability of biologic protein products, particularly for the purposes of product registration purposes are discussed as well as an overview of ICH Q5C Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products. Stability protocols should be designed keeping in mind the idiosyncrasies of biologics as well as formulation, analytical, manufacturing, and regulatory knowledge gained during development.