Common deficiencies in generic drug product development

Any generic medicine must perform the same in the body as the brandname innovator medicine (RMP/RLD) and as such it must be the same with regards to dose, dosage form and route of administration, safety, effectiveness, strength, and labeling (with certain limited exceptions). It must also meet the same high standards of quality and manufacturing as the reference product and in some cases higher due to the age of the reference product and the characterisation techniques used at the time. In addition, it must be taken and used in the same way. Nevertheless, generic medicines tend to cost less than the RMP/RLD because these products do not have to go through the rigorous animal and clinical (human) studies that were required of the reference product to demonstrate safety and effectiveness. Ultimately, this means that, on average, generic medicines are sold at up to 85% less than their reference product counterpart. Thus, for generic products the concept of bioequivalence is fundamental; crucially, the guidance to achieve bioequivalence between reference and generic products depends upon the route, type and complexity of the RMP/RLD requiring only a demonstration of pharmaceutical equivalence in some cases, or a detailed therapeutic equivalence study with a clinical endpoint in others. Recently, regulatory guidance for the development of topical generics highlights some of the issues that have arisen for all dosage forms. Specifically, the US Food & Drug Administration (FDA) has focused primarily on a Product Specific Guidance approach whereas the EU and UK have a draft universal guidance that covers the majority of topical products. This chapter focuses on differences between the two, contradictions and areas for potential improvement.