By Dr. Shuang Chen, Ph.D.
Senior Principal Scientist, AbbVie

In recent years, more and more structurally diverse and complex molecules have been developed to tackle difficult but attractive drug targets, such as protein-protein interactions. In the case of disease eliminating direct-activity antivirals for hepatitis C that target different stages of the viral life cycle through multiple mechanisms of action, their molecular diversity and complexity increase unavoidably. Consequently, these molecules have posted some great challenges in pharmaceutical development including unfavorable physiochemical and biopharmaceutical properties, complex solid form landscape, more constrained crystallization conditions, and less desirable crystal properties. In this presentation, these solid form and crystallization related development challenges and probable solutions thereof will be illustrated through the case studies of the 1st and 2nd gen HCV drugs dasabuvir, ombitasvir, and glecaprevir. Learnings from the studies can be useful in building deep understanding on solid state properties and performance relationship of crystalline forms of complex drug molecules and for developing their efficient and robust crystallization and isolation process.