Interchangeability. An insurmountable fifth hurdle?

Abstract

The arrival of biosimilars has led to considerable debate on how they can be used in clinical practice. A particular concern is related to the question of whether a biosimilar can be safely interchanged with the originator product or other biosimilars. Here we will discuss challenges to the regulatory approach for establishing interchangeability, in the sense of considering biosimilar versions as therapeutic equivalents that could - depending on National or Federal Law - be substituted at the pharmacy level, and compare these to the weight of real-world evidence of the risks of potential differences that could modify longer-term clinical benefit-to-risk. Our discussion will be mainly focused on monoclonal antibodies. We conclude that it will be highly challenging to establish interchangeability of biosimilars, and it should be questioned whether the 'higher' standard required for designation of interchangeability adds to the benefit for patients.