CURRENT OPINION The Diversity of Biosimilar Design and Development: Implications for Policies and Stakeholders

Abstract

The Author(s) 2015. This article is published with open access at Springerlink.com Abstract Biosimilars are required to be similar or highly similar in structure to their biologic reference product but are neither expected nor required to contain identical active substances. For example, glycosylated biosimilars approved to date demonstrate quantitative and qualitative structural differences from their reference product and exemplify the latitude of variations permitted for biosimi-lars. Although differences between a candidate biosimilar and its reference product will be evaluated for differential clinical effects during biosimilarity assessment, it is unli-kely that potential differences between any two indirectly related biosimilars will be formally evaluated. Further-more, biosimilar pathways permit variations in pharma-ceutical attributes, clinical development approaches, and regulatory outcomes, resulting in further diversity of attributes among approved biosimilars. Because biosimi-lars may vary across the ranges of structural and functional acceptance criteria, they should not be treated like multi-source, generic drugs. Key Points Although biosimilars are highly similar to their reference products, they are not identical to them. Regulatory pathways permit slight differences in structural and other product quality attributes of biosimilars; such difference are unlikely to be formally evaluated among indirectly related biosimilars, resulting in a potential for a broader range of potential differences in quality attributes among approved biosimilars. Policies and practices related to the identification and use of biosimilars should take into account potential molecular differences among multiple biosimilars of the same reference product and should not treat them like generics. Specific recommendations to distinguish biologics from generic drugs in practice include ensuring that all biologics have distinguishable names and are prescribed by a distinguishable name, that a clinician is involved in decisions to switch among non-interchangeable biologics, and that patient medical records track biologics by their distinguishable names.