Biosimilars: new insights into the regulatory approval process in Europe

In a paper published very recently by our researcher Johanna Mielke, based at Novartis (Mielke et al. (2018), some insights are given into the clinical development strategies used to obtain approval for proposed biosimilars and how these have been assessed by the EMA (European Medicines Agency).  It is clear that, despite the availability of overarching and product-specific EMA guidelines, variability is present not only in the clinical development strategies used by sponsors to gain approval but also in the way the submissions are assessed by the EMA.

A biosimilar is meant to be a cheaper copy of a biologic drug whose patent has expired. The EMA formally defines a biologic as a “medicine that contains one or more active substances made by or derived from a biological source”. Biologics have revolutionised the treatment of patients in important areas like cancer, diabetes and inflammatory diseases.

One possible reason for this variability is that the guiding principle for biosimilar approval in Europe is based on the concept of the totality of the data. This means that there is not one pivotal step or study in the development program, but all information is considered important and the final decision as to whether a product is approved or not is based on all provided data (i.e., on an analytical quality assessment and non-clinical and clinical data). In particular, it is possible to gain approval even in cases in which a single study or a single analysis has failed as long as justification is provided.

Even for submissions where product-specific guidelines were available at the time of development, these were not necessarily followed. A case is identified where it seems that the sponsor had a strong opinion that was incompatible with the guidelines. The sponsor decided to pursue an approach for the clinical development that contradicted the guideline that was in operation at the time of development in most points. Nevertheless, the sponsor gained approval.

Mielke et al. (2018) also discuss how the European public assessment reports (EPARs) could be improved and recommend that a CONSORT-like statement for reporting guidelines for EPARs should be implemented. To facilitate this they propose a checklist specific for EPARs related to biosimilars.

We note that, at the time of writing, there are 41 approved biosimilars in Europe. A systematic review of the EPARs for biosimilars that gained approval prior to August 2016 is described in Mielke at al. (2016).


Mielke J, Jilma B, Jones B and Koenig F (2018).  An update on the clinical evidence that supports biosimilar approvals in Europe. British Journal of Clinical Pharmacology, Accepted Article:

Mielke J, Jilma B, Koenig F and Jones B (2016). Clinical trials for authorized biosimilars in the European Union: a systematic review. British Journal of Clinical Pharmacology, 82(6), 1444-1457.