Interchangeability for Biologics is a Legal Distinction in the USA, Not a Clinical One

Abstract

Biologics are increasingly vital medicines that significantly reduce morbidity as well as mortality, yet access continues to be an issue even in apparently wealthy countries, such as the USA. While patient access is expected to improve with the introduction of biosimilars, misperceptions in a significant part based on terminology continue to make a sustained contribution by biosimilars difficult. Patients are and will continue to suffer needlessly if biosimilars continue to be impugned. Consequently, it is increasingly urgent that semantics are clarified, and in particular, the implication that interchangeable biologics are better biosimilars dismissed. This paper distinguishes between the real differences between biologics that matter clinically to patients and discusses the actual meaning of a US Food and Drug Administration designation of interchangeability for a biosimilar product. This will help highlight where there is need for further Food and Drug Administration education and which stakeholders likely need that education the most.

Future Evolution of Biosimilar Development by Application of Current Science and Available Evidence: The Developer’s Perspective

“…Given the tight controls already in place on immunogenicity and experience accrued to date, we believe that a multiple-switch study to obtain the unique legal designation of US interchangeability is not warranted [ 13 ], and indeed has already been waived by FDA when justified (e.g., insulin glargine and ranibizumab biosimilar products) [ 63 , 64 ]. Indeed, based on the knowledge and experience already obtained, it is now possible to eliminate multiple-switch PK studies currently required for the separate US category of interchangeability without impacting patient safety or efficacy.…”

“…The potential for increased or different immunogenicity was one of the foremost concerns when the biosimilar development pathway was first developed. This in turn led to the US Food and Drug Administration (FDA) to recommend performing a multiple-switch study to obtain the additional, optional, US legal designation of “interchangeable biologic” for a given biosimilar [ 12 , 13 ]. While immunogenicity data should always be collected for both biosimilars and novel biologics, to date, the immunogenicity levels elicited by biosimilars approved by the FDA and European Medicines Agency (EMA) have reliably matched the immunogenicity of their reference products [ 9 – 11 , 14 – 16 ].…”