Biosimilar: what it is not

Abstract

A biosimilar is a high quality biological medicine shown to be in essence the same as an original product. The European Medicines Agency (EMA) paved the way in the regulatory arena by creating a safeguarding framework for the development of biosimilars. Biosimilar is thus a regulatory term that alludes to the evidence-based studies required to demonstrate such very high similarity. They are therefore not innovative products but the pathway laid down by the EMA for their approval represented a new paradigm. This has brought some confusion and has cast doubts among healthcare professionals about the scientific evidence behind their authorization. Many papers have been published to clarify the concept, and to reassure those professionals, but misconceptions frequently still arise. Unfortunately, this prevents biosimilars from deploying their full therapeutic added value. This paper is intended to approach those misconceptions from a new angle, by explaining what a biosimilar is not…and why. A biosimilar is neither a generic, nor an original product. It is not a biobetter or a 'stand-alone'. Therefore, it should not be managed as such therapeutically, commercially or from a healthcare policy viewpoint. The EMA's criteria were acknowledged by other agencies, but a significant regulatory gap with a vast majority of regulatory bodies still remains. This leaves room for the so-called non-original biologics (NOB), i.e. non-biosimilar biologics, to be launched in many regions. Raising awareness of what a biosimilar is and what it is not, will generate trust in biosimilars among healthcare professionals and will ultimately benefit patients.

Keywords: biobetter; biologic; biosimilar; biotechnology-derived medicine; generic; non-original biologic.

Figure 1

Conceptual discrimination between biosimilar and non-biosimilars on the basis of regulatory and non-regulatory criteria. Only products claimed to be highly similar to a reference original biologic, and whose similarity is demonstrated through a thorough EMA-like comparability exercise should qualify as biosimilars. (This figure is not intended to be an accurate account of the available alternative regulatory pathways). *API = Active Pharmaceutical Ingredient or Active Substance **EMA regulatory standard = European Medicines Agency's biosimilar application pathway criteria, or alternatively, equivalent criteria US FDA, Health Canada, Japanese PMDA, or Australian TGA

Figure 2

Comparative EMA requirements for biosimilar development vs. studies envisaged for generics, original products, and possibly biologics after manufacturing changes. The regulatory requirements rely to a large extent on the background knowledge sustaining the product development. In the case of a fully original biologic application, there is no accumulated evidence prior to undertaking the development programme. Hence a complete dossier will be requested. It is to note that, given the particularly high sensitivity of structural and biological activity studies for picking up potential differences, the biosimilar quality module is the most extensive. Finally, it has to be borne in mind that this is a general framework. The actual specific requirements will need to be established on a case-by-case basis ^*API = Active Pharmaceutical Ingredient or Active Substance