Clinical data requirements for biosimilars in the EU: analytical comparability

Biosimilares/Investigación | Posted 18/10/2019 post-comment0 Post your comment

For biosimilars, the regulatory review process is based on the totality of evidence generated in support of biosimilarity.

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The biosimilar clinical programme aims to demonstrate that the proposed biosimilar is similar to the originator biological based on analytical assessments, and that it does not have clinically meaningful differences from the originator biological, based on comparative clinical studies.

In their article [1], authors from the Paul-Ehrlich-Institut, the European Medicines Agency (EMA) and the Federal Institute for Drugs and Medical Devices (BfArM), discussed the totality of evidence approach for biosimilars in the European Union (EU) using case studies to illustrate biosimilars for which differences were observed in different parts of the comparability exercise and on the justification for why these differences did not preclude regulatory approval.

Analytical comparability
In the case of an infliximab biosimilar, extensive analytical tests showed physicochemical and structural comparability except for a small difference in the proportion of afucosylated forms. However, this difference disappeared under more physiological conditions, e.g. when serum was added or peripheral blood mononuclear cells were used as effector cells, suggesting that the observed difference in FcγRIIIa binding was not relevant in vivo. These differences were confirmed not to be clinically relevant in a large pharmacokinetic (PK) study in patients with ankylosing spondylitis and a large phase III equivalence trial in patients with rheumatoid arthritis (RA).

All indications of the reference product were approved in the EU and in the US but initially not in Canada. However, Health Canada’s decision was reversed in 2015 based on additional functional data and the totality of evidence [2].

The authors of the research paper [1] declared that the views and opinions expressed in the paper are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agencies with which the authors are affiliated.

Conflict of interest
The authors of the research paper [1] declared that there was no conflict of interest.

Editor’s comment
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1. Wolff-Holz E, Tiitso K, Vleminckx C, Weise M. Evolution of the EU Biosimilar Framework: past and future. BioDrugs. 2019 Sep 20. doi: 10.1007/s40259-019-00377-y. [Epub ahead of print]
2. GaBI Online - Generics and Biosimilars Initiative. Health Canada approves Inflectra biosimilar for extra indications []. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Oct 18]. Available from:

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