European medicines agency guideline for biological medicinal products: a further step for a safe use of biosimilars

Allergists and clinical immunologists welcome the recent revision of the guideline on similar biological medicinal products containing biotechnology-derived proteins (“biosimilar”) that the European Medicines Agency (EMA) has published on December 18, 2014 [1]. In the past justifiable doubts on an uncritical use of biosimilars have been formulated by most scientific societies, including our Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Perplexities were linked to the fact that relatively small changes in manufacturing, characterization and/or formulation of a biological medical product can significantly alter its efficacy, safety and/or immunogenicity [2]. This is particularly relevant when we consider the possible use in clinical practice of biosimilar monoclonal antibodies. Indeed, the previous EMA guidelines addressed manufacturing, not clinical pharmacology, toxicology, pharmacokinetic, pharmacodynamic and clinical considerations. It is sufficient to consider how changes in the cell line that produce the monoclonal antibody and/or post translational modifications, including glycosylation patterns, could alter the specificity of the target antigen binding and the effector functions of the new biosimilar. For instance, the drug cytotoxic activity or those functions that are mediated by FcγR interactions may be in theory altered by the culture conditions. Minimal changes in the production process of the biosimilar could also result in cross linking and formation of aggregates which have been described to activate B cells in Tcell independent way. Furthermore, small alterations in the manufacturing process might impact not only the half-life of the product but also its affinity and avidity, or its dose-response efficacy. Obviously, there are advantages in using biosimilars and the economic savings is considered the most important, in particular for those