Demonstration of biosimilarity, extrapolation of indications and other challenges related to biosimilars in Europe.

The regulatory framework for biosimilars was established across Europe in 2005 based on the concept of biosimilarity. This legislation secures the manufacturing, evaluation, and market authorization (MA) of high-quality safe and efficacious biopharmaceuticals that are highly similar to their reference medicinal product (biosimilars). Demonstration of biosimilarity is documented by full-scale comparability exercises between the biosimilar and the reference product at quality, preclinical, and clinical level. However, the complexity, diversity, and heterogeneity of biosimilars, both in structure and manufacturing, combined with the scientific knowledge accumulated in biotechnological analysis of recombinant therapeutic proteins requires continuous improvement of the regulatory framework based on the evolution and experience gained in this field. This current opinion article presents the concept of biosimilarity, discusses the extrapolation of indications that is acceptable based on a case-by-case basis by CHMP/EMA and uncovers other challenges lying ahead in the development of biosimilars. Biosimilars are still quite 'young' products that require worldwide attention.