An update on the clinical evidence that supports biosimilar approvals in Europe.

Franz Koenig,Johanna Mielke,Byron Jones,Bernd Jilma

doi:10.1111/bcp.13586

Abstract

AimSponsors and regulators have more than 10 years of experience with the development of biosimilars in Europe. However, the regulatory pathway is still evolving. The present article provides an update on biosimilar development in practice by reviewing the clinical development programmes of recently approved biosimilars in Europe.MethodsWe used the European public assessment reports (EPARs) which are published by the European Medicines Agency (EMA) for a comparison of the clinical development programmes of the 37 approved biosimilars in Europe. Here, we present novel strategies in the development of biosimilars by focusing specifically on the 17 biosimilars that have gained approval in the last year, but we also compare additional key characteristics for all approved biosimilars.ResultsThe high variability of the clinical development strategies that we found previously was confirmed in the present analysis. Compared with earlier biosimilar applications, more nonstandard development strategies have been used recently. This includes, for example, applications without any studies in patients, and more complex study designs. During this study, we found that the EPARs for biosimilars seem to be improving; however, we identified important details which were still often missing. We provide a proposal for a checklist of the minimum information that should be included in biosimilar EPARs for giving the general public insights into the rationale for the approval of biosimilars.ConclusionsEuropean regulators still seem to be open to consider approaches that differ from the guidelines or previous applications, as long as justification is provided.

Highlights

As with a generic drug, a biosimilar is developed and approved as a copy of an already marketed product that has lost its patent protection
We investigated how the guidelines provided by the European Medicines Agency (EMA) are put into practice by conducting a systematic review of the clinical development programmes of the 21 biosimilars that had been approved in Europe at the time of acceptance of our first systematic review [7]
In the study presented in this paper, we examined recent developments in clinical biosimilar development by looking at novel trends in the planning and analysis of the clinical trials of the 17 biosimilars that had been approved since the acceptance of our previous systematic review in August 2016 [7]

Summary

Introduction

As with a generic drug, a biosimilar is developed and approved as a copy of an already marketed product (the reference product) that has lost its patent protection. As the reference product for a biosimilar is a biological molecule (‘biologic’) instead of a small-molecule drug, even though the main concept of biosimilars and generics is comparable, there are some fundamental differences: biosimilars are much more complex and they are produced in living cells [1]. This makes the product sensitive to small changes in the production environment, so that even for the originator company that possesses most knowledge about the reference product, it would not be possible to produce an exact copy. The abbreviated development programme that is used for the approval of generics is not adequate for biosimilars, and more evidence is required [3]

Objectives

Methods

Results

Conclusion