Biosimilars: Review of regulatory, manufacturing, analytical aspects and beyond

Abstract

Biologics have more complex production processes compared to small-molecule drugs. They may even prove labile when drifting from batch-to-batch or in different production locations. The development of new similar biological product was regulated early to face the relevant challenges of this industry. As a result, since 2006 biosimilars were introduced to biotechnology arena with a massive competition in pharmaceutical industry. In this review, the aspects related to similarity testing of biosimilars to the original biological products are discussed involving manufacturing challenges to ensure the quality, safety, and efficacy of these products to the patient health. Immunogenicity studies are highlighted as an important part of the safety assessments. Additionally, several analytical methods that are usually used to evaluate biosimilars in comparison to their reference biologic are summarized and categorized in terms of the intended physicochemical and biological characterization. On the other hand, the international efforts of several regulatory agencies including the European Medicines Agency, World Health Organization and United States Food and Drug Administration for biosimilar development are discussed according to updated revised guidelines.