Development Pathways for Subcutaneous Formulations of Biologics Versus Biosimilar Development

Introduction: Biologics are highly complex drugs and many of their characteristics are defined by the manufacturing process. In recent years, several monoclonal antibody (mAb) biologics, which were hitherto only available for intravenous (IV) administration, have been reformulated for subcutaneous (SC) administration. Reformulation involves alterations to the established manufacturing process and it has been argued that a SC formulation should therefore be considered a biosimilar version of its previously approved IV formulation. Areas covered: Developing an SC version of an approved IV mAb product requires the adaptation of its formulation and route of administration. This process is illustrated via case examples of trastuzumab and rituximab and summarize what data requirements support the regulatory approval of these new formulations. Furthermore, we discuss similarities and differences between the development of an SC product vs. the development of a biosimilar. Expert opinion: The production process of a biosimilar is independently established from the very beginning, while the development of an SC formulation affects later stages of an already established production process and builds on extensive experience with the IV formulation. Considering these fundamentally different situations, a biologic product reformulated for SC administration should not be considered a 'biosimilar' version of itself.