Biologics and Biosimilars: A Comprehensive Review of Development, Regulatory Environment, and Safety Surveillance

Abstract

Biological medicines, first developed in the 1980s, have fundamentally altered modern medical practice, utilizing biotechnological production in living systems to provide targeted therapies for complex and serious diseases such as cancer and autoimmune diseases. While biologics are different from drugs that are chemically synthesized, biologics also require alternative regulatory processes as a result of their large and complex molecular structure. Following the patent expiration of biologics, biosimilars have become available as low-cost competitors that provide patients with access to these innovation-based therapies. This comprehensive review describes the development, regulatory pathways, and post-marketing safety monitoring of biosimilars, while also clarifying the distinctions and similarities between biosimilars and related products, including intended copies, biobetters, and individual biologics. This review describes the accelerated regulatory process and summarizes the comparative research articles that are required by regulatory agencies, including EMA and FDA, including the analytical, non-clinical, and clinical comparative studies. This review details pharmacovigilance systems that provide important post-marketing safety monitoring for biosimilars, specifically around the topic of immunogenicity. Controversies with biosimilars, including extrapolation, interchangeability, and substitution, were also critically evaluated to identify current controversies and issues, regional policy variations, as well as identify direction and opportunities for the future. While there are still challenges, including the harmonization of regulatory frameworks and the need for all stakeholders to come to consensus on these frameworks, continual advances in manufacturing and analytics hold promise for greater consistency across biosimilars. By summarizing areas of recent literature, this review offered many potential takeaways for clinical practice, healthcare decision-making, and healthcare policy, while also highlighting the importance of biosimilars as a way to balance innovation and affordability.