Biosimilar mAb development – quality similarity considerations

Biosimilars/Research | Posted 26/11/2021 post-comment0 Post your comment

Since 2013, when the first biosimilar monoclonal antibody (mAb) was approved by the European Medicines Agency (EMA), the number of approved biosimilar mAbs has been increasing dramatically [1]. The large number of approved biosimilar mAbs in both the European Union (EU) and the US makes the evaluation of these applications possible from a product quality perspective.

Quality, similarity and safety V13D12

Author Zoltán Urbányi therefore carried out an analysis of 23 biosimilars of six different reference medicinal products (RMPs) [2]. Quality assessments of biosimilars of the drugs adalimumab, bevacizumab, etanercept, infliximab, rituximab and trastuzumab, from both EMA and the US Food and Drug Administration (FDA), were evaluated.

The development of biosimilar mAbs is a strictly regulated process that starts with the identification of critical quality attributes through a risk-based approach and by determining the comparability ranges measuring the relevant quality parameters of dozens of batches of RMPs.

The quality parameters of a biosimilar mAb are influenced by a series of process parameters. The first, cell line development, is a very critical step that has a major influence on the final quality of the product. The subsequent steps in drug-substance and drug-product manufacturing processes, which must be strictly controlled, determine the final quality of the product.

The quality similarity of the reference product and the biosimilar candidate must be demonstrated during the marketing authorization phase. This quality similarity assessment must cover all structural and biological-functional quality attributes of the active pharmaceutical ingredient. The quality aspect of the totality of evidence consists of three, closely related considerations. The physicochemical field covers both identity/structure and purity/variant aspects, which in turn cover the structure (both primary and higher order) of the protein, post-translational modifications, other chemical modifications and degradation products. Biological-functional aspects of quality cover all binding and cell-based features of the molecule, depending on its mode-of-action. The structure-activity relationship provides the link between the physicochemical and biological-functional field and provides information on the clinical relevance of some potential differences in the structure or the composition of variants.

As is demonstrated in the research paper [2], minor quality differences can always be found, as the production of a fully identical biosimilar mAb is theoretically impossible. In all cases, the applicant should be able to demonstrate that the identified differences have no influence on the pharmacokinetics, efficacy, safety and immunogenicity of the biosimilar candidate, through a comprehensive evaluation of all quality, non-clinical and clinical data based on the totality of evidence, and that as a result, these minor differences should be deemed negligible, i.e. not of a nature as to preclude biosimilarity in any of the evaluated cases.

Conflict of interest
The author of the research paper [2] did not provide any conflict-of-interest statement.

Abstracted by Zoltán Urbányi, Biotechnology Research Department, Gedeon Richter, Budapest, Hungary.

Editor’s comment
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Quality, similarity and safety of biosimilars

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1. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe []. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Nov 26]. Available from:
2. Urbányi Z. Quality similarity-driven development of biosimilar monoclonal antibodies. Drug Discovery Today: Technologies 2021; Available online 19 June 2021.

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