Abstract

Although the development of complex generic products has been increasing in recent years, the regulatory pathway and characterisation requirements have not always been clear. For example, there are some instances where abbreviated new drug applications under the 505(j) pathway would not be appropriate, and the complex product will require the 505(b)(2) procedure for approval.

This article highlights the complex generic products definition and classification, the current status of US Food and Drug Administration (FDA) guidance, and provides two case studies for challenges encountered in complex generic product development. The case studies, focusing on long-acting injectables and semi-synthetic peptides, highlight the challenges and provide details on the approach to demonstrate comparability with the Reference Listed Drug (RLD). Ultimately, the goal is to minimise the need for clinical bioequivalence studies through thorough physicochemical and/or bioassay characterisation studies.