Bioequivalence for Liposomal Drug Products

Abstract

Liposomal drug products often pose a challenge in demonstrating bioequivalence between generic and brand name products. After administration, the active pharmaceutical ingredient in a liposomal drug product usually exists in multiple forms in plasma (e.g., free drug and encapsulated drug). The products often have physical and chemical properties that critically impact therapeutic effect and safety profile. Many of these critical physicochemical properties need to be characterized by a distribution. Liposomal drug products also exhibit complex in vivo release patterns that are affected by the liposome vesicles, drug substance, and inactive ingredients. Consequently, to demonstrate bioequivalence, it is important to identify the most physiologically relevant analyte(s) for BE purposes, conduct comprehensive, comparative physicochemical testing on a wide range of product properties, and perform in vitro release testing under controlled, physiologically relevant conditions. This chapter reviews scientific literature for characterizing different types of liposomal drug products. Using PEGylated liposomal doxorubicin hydrochloride injection as an example, this chapter will discuss the challenges and solutions in determining the proper bioequivalence recommendations for specific liposomal drug products.