Ocular emulsions and dry eye: a case study of a non-biological complex drug product delivered to a complex organ to treat a complex disease

Generic drugs are intended to provide a lower cost option of safe and eff ective medicines thereby granting greater patient access to aff ordable health care. A sound scientifi c basis and a robust regulatory process to demonstrate bioequivalence of the generic version of a branded drug are critical to ensuring the success of this option. In establishing the scientifi c basis for testing methods, the nature of the branded drug, the disease and site of action(s) must be considered. While the regulatory paths for establishing bioequivalence are well understood for small molecules, in particular those administered orally, and recently for biosimilars, the path for non-biological complex drugs (NBCDs) is an emerging area. Similarly, the use of systemic pharmacokinetic (PK) or PKpharmacodynamic (PK-PD) measures in clinical studies to demonstrate bioequivalence is well established for drugs that are delivered to the site of action via the systemic circulation. Conversely, locally administered and locally acting drugs present unique challenges. For locally acting drugs, the disease and the aff ected organ introduce complexity when considering drug delivery and drug absorption. Eff orts to establish a scientifi cally sound regulatory path for demonstrating bioequivalence or similarity to RESTASIS® present an example where the complexities of drug, disease and organ meet to create a multifaceted challenge. This paper reviews the current state of our understanding of NBCDs, and uses the RESTASIS® case study to illustrate current gaps in knowledge that create diffi culties in the design of a robust regulatory path to establish bioequivalent NBCDs.