Review of Quality Attributes and Analytical Methods Used for Comparative Analytical Assessment of Monoclonal Antibodies as Part of Successful Biosimilar Approvals in the United States and European Union.

Monoclonal antibodies (mAbs) have revolutionized therapeutic treatments by their ability to target specific antigens, leading to enhanced clinical outcomes over other drugs. They are one of the largest modalities within the growing biotherapeutics space and are indicated for a range of diseases. Though transformative, mAbs are still not readily accessible to many patients globally because of their high costs. An increasing number of mAbs are losing patent exclusivity, which has opened the door for the development of biosimilars that could drive down costs and ensure increased access to these life-saving drugs. Regulators approve biosimilars after conducting a rigorous evaluation similar to any other biologic medicine to ensure the safety, quality, and efficacy of these products. To establish biosimilarity, extensive comparative analytical and clinical studies of the biosimilar product with the approved reference product is a regulatory expectation. Growing acceptance from regulators to potentially waive clinical efficacy studies when robust evidence for similarity with reference product is established from analytical, functional, and pharmacokinetic/pharmacodynamic studies will have a major impact on reducing the time and cost of developing biosimilars. Comparative analytical assessment includes side-by-side analysis of the biosimilar with the reference product to demonstrate similarity regarding their physicochemical and functional characteristics. This is usually achieved by identifying product quality attributes (PQAs) that could impact clinical safety and efficacy and applying orthogonal analytical methods to characterize these attributes to identify any differences between the products. This review identifies the common PQAs studied for approved mAb biosimilars in the United States and the European Union through to the end of 2024. We have also compiled the data for the analytical methods used to characterize these attributes and identified a subset of methods universally used among biosimilar applicants. Finally, a brief overview of the risk-based analysis of attributes is summarized from the regulatory submissions.