Biosimilars: Concepts and controversies Gámez-Belmonte, Reyes Hernández Chirlaque, Cristina Arredondo Amador, María Aranda Clemente, Carlos José González Pérez, Raquel Martínez Augustín, María Olga Sánchez De Medina López-Huertas, Fermín Biosimilars Comparability exercise Extrapolation of indications This work was funded by the Ministerio de Economía y Competividad (BFU2014-57736-P, AGL2014-58883-R), Junta de Andalucía (CTS164, CTS235). RGB, CHC, MAA and CJA are funded by Ministery of Education. CHC and CJA were additionally funded by the Contrato Puente program of the University of Granada (Plan Propio). CIBERehd is funded by the Instituto de Salud Carlos III. Biosimilars are copies of reference biological drugs, developed as the patents for original biologicals expire. They are thus developed to replicate an original biological medicine just a generics are intended to replicate a chemically-synthesized medicine; however, there are important technical and regulatory differences between the two. Unlike chemical drugs, molecular identity cannot generally be established for any two biological drugs. Accordingly, their pharmacological properties cannot be assumed to be the same. This is due to the complexity of the production of biologicals and to the presence of minor natural variations in the molecular structure (collectively known as microheterogeneity). Further, biological production yields slightly different versions of the drug over time, particularly when changes are introduced in the production process. In this case the prechange and postchange versions of the biological are analyzed in what is called a comparability exercise. The comparable versions thus validated are considered not to have any significant differences at the clinical level. Likewise, biosimilars are not identical copies but comparable versions of the original biological drug, also validated through a comparability exercise, although of a much broader scope. Although current knowledge about biosimilars has increased significantly, they still arise a number of controversies and misconceptions, particularly regarding issues like extrapolation of indications, immunogenicity and substitution. This review deals with concepts and controversies in the biosimilar field. 2026-01-16T07:50:36Z 2026-01-16T07:50:36Z 2018 journal article Publisher version: Gámez-Belmonte R, Hernández-Chirlaque C, Arredondo-Amador M, Aranda CJ, González R, Martínez-Augustin O, Sánchez de Medina F. Biosimilars: Concepts and controversies. Pharmacol Res. 2018 Jul;133:251-264. doi: 10.1016/j.phrs.2018.01.024 1043-6618 1096-1186 https://hdl.handle.net/10481/109770 10.1016/j.phrs.2018.01.024 eng open access Elsevier