Comparing Originator Biologics and Biosimilars: A Review of the Relevant Issues.

PURPOSE: We provide a review of current knowledge on comparability between biosimilars and originator biologics in view of the continuous evolution occurring in this highly dynamic area.

METHODS: English-language literature indexed in MEDLINE was explored, without time limits, to July 31, 2016, using the terms biosimilar, biotechnologic drug, biologic drug, monoclonal antibody, fusion protein, and anti-tumor necrosis factor. The reference lists of identified articles were examined carefully for additional pertinent publications.

FINDINGS: Biological medicines are much more structurally complex and extremely sensitive to manufacturing conditions and therefore more difficult to characterize and produce than small molecule drugs. Even minor changes in manufacturing may lead to significant variations of the cellular systems used for biological production, as well as to differences in the structure, stability, or other quality aspects of the end product, all of which have the potential to affect tolerability and/or efficacy and increase the risk of immune responses. Owing to these issues, specific regulatory guidance on biosimilars is continuously evolving, and there is some disagreement on which studies need to be implemented to approve a biosimilar. According to current literature, the following points on biosimilars deserve consideration: biosimilar development is characterized by global harmonization, although several not fully answered questions remain regarding extrapolation of indications, switching or interchangeability, and tolerability; in patients with rheumatic diseases, the tolerability and efficacy of biosimilars in clinical practice remain to be established; several medical and patient associations have published position papers on biosimilars requesting that safety, efficacy, and traceability be carefully considered; long-term postmarketing studies should be implemented to allow physicians to gain confidence in biosimilars.

IMPLICATIONS: On the basis of current knowledge, and taking into consideration both regulatory rules and medical society positions, it can be concluded that, although cost savings are highly desirable, the approval process for biosimilars needs to place tolerability and efficacy, supported by scientifically sound evidence, as the highest priority. Moreover, physicians must retain full authority regarding the decision about which biopharmaceutical to use for treating patients.