Biosimilars and interchangeability: Regulatory, scientific, and global perspectives

Biological medicines, biologics have transformed the treatment of many serious diseases but are often costly. As patents expire on original biologics, biosimilars have emerged to improve access. A biosimilar is generally defined as a biologic product that is highly similar to an already authorized biologic,the reference product, with no clinically meaningful differences in safety, purity, or efficacy. Because biologics are made in living systems and naturally variable, a biosimilar cannot be an exact copy of its reference; instead, it is developed through a rigorous comparability process to ensure it matches the reference product’s critical attributes within an acceptable range. If successful, biosimilar should perform just as safely and effectively in patients as the original product. This article reviews the scientific basis of biosimilars and the concept of interchangeability, global regulatory frameworks (EMA, FDA, WHO), key requirements for analytical comparability, pharmacokinetic/pharmacodynamic studies, immunogenicity assessment, criteria for interchangeability (including switching studies and post-approval surveillance), and real-world evidence on the safety of biosimilar substitution. Relevant regulatory guidelines and recent literature are cited throughout to provide an up-to-date, scholarly overview.