The road from development to approval: evaluating the body of evidence to confirm biosimilarity.

Biosimilars are products that contain a similar version of the active substance of an already authorized original biologic medicinal product (reference medicinal product). Their development requires special consideration, as similarity to the reference agent needs to be established through a comprehensive comparability exercise. Given the complex nature of these agents, minor structural differences may emerge, but the process of biosimilarity determination is designed to ascertain that the nature and impact of these differences are not clinically significant. Determination of biosimilarity should follow quality-by-design principles, which provide a deep understanding of the product development process, guided by pre-defined objectives, process control and risk management. Compared with novel biologic development, biosimilar development places greater emphasis on establishing preclinical quality characteristics. Determination of comparability of quality characteristics includes assessment of physicochemical properties, biological activity, immunochemical properties, purity, impurity and quantity, with appropriate in vivo pharmacology studies being conducted thereafter. Head-to-head comparisons are then conducted to determine pharmacokinetic and pharmacodynamic characteristics, and efficacy, safety and tolerability in phase I and phase III clinical studies. Post-approval risk management requirements include implementation of pharmacovigilance systems and risk management through, for example, the conduct of pharmacoepidemiological studies. There are several biosimilars used in the field of rheumatology that are available in the European Union, or in development, that offer the potential to increase affordability/accessibility of biological treatment. The role of these agents in rheumatology will be determined by the confidence placed in them by rheumatologists. These prescribers should expect high-quality data evaluated by an extensive assessment process.