Pharmacovigilance of Biosimilars: Global Experience and Perspective

Abstract

This chapter reviews important aspects of pharmacovigilance of biosimilars. Biologics are structurally complex molecules that are more difficult to characterize, produce, and reproduce than most small-molecule compounds. Ongoing robust pharmacovigilance is critical in the monitoring, detection, and assessment of safety signals over the life cycle of every biologic. The availability of multisource biologics, including biosimilars, warrants rigorous pharmacovigilance to accurately detect and disaggregate safety signals. Although biosimilars are highly similar to their reference biologics, they are not required or expected to be identical, and regulatory pathways permit slight variations in structural and pharmaceutical attributes and clinical development approaches. During development, candidate biosimilars are evaluated in a stepwise manner against their reference product for similarity in structure, function, clinical efficacy, and safety. However, clinical studies to evaluate biosimilarity may not detect rare adverse events, and potential differences in safety resulting from minor differences in manufacturing procedures between a biosimilar and its reference product (or other biosimilars) may not be detected before approval. Risk management plans, particularly during the early postmarketing period, are also an important component of pharmacovigilance planning for biosimilars. Important components of pharmacovigilance programs include ongoing and rigorous data collection, adverse event reporting, and analysis of causal relationships resulting in accurate attribution of an adverse event to the correct product. Methods to improve product-specific monitoring, like the assignment of distinguishable nonproprietary names for all biologics and the use of additional product identifiers (e.g., batch number, trade name, manufacturer) for adverse event reporting, are vital to ensure accurate surveillance and traceability of all biologics, including biosimilars.