Novel Perspectives on Biologics and Biosimilars: History, Gaps and Future Advancements

Abstract

Biologics have greatly changed the narrative in oncology, immunology, endocrinology, and dermatology practices. Biosimilars, which are highly similar to high quality approved biologics, provide sustainable access and competition. This review evaluated important historical events, regulatory frameworks (EMA, FDA, WHO), therapeutic uptake, market constraints, methodology aspects (analytical similarity, extrapolation and interchangeability), covigilance requirements, and emerging spaces (biobetters; bispecifics; ADCs; AI for development; manufacturing 4.0). We draw upon evidence from key reviews and policy analysis to identify areas for which continued gaps exist—long-term safety and immunogenicity; pharmacovigilance transparency; international regulatory inconsistency; patient and clinician acceptance—and advocate for a research agenda to improve, equitable, patient-centered availability of biologics and biosimilars.

Introduction

Biologics are complex therapies produced in living systems, including monoclonal antibodies, recombinant proteins, and vaccines. Biosimilars are highly similar versions of licensed biologics with no clinically meaningful differences in safety, purity, or efficacy. Their rise is driven by advances in analytical technologies, regulatory frameworks, and economic pressures to improve access to high-cost therapies.

The regulatory landscape varies: the EMA uses a stepwise comparability approach, the FDA applies a totality-of-evidence paradigm, and the WHO provides guidance for harmonization, with differences in interchangeability, naming, traceability, and extrapolation across regions. Analytical advancements—like mass spectrometry, glycan profiling, and bioassays—enable risk-based clinical assessment and reduce the need for extensive trials.

Biosimilars have been widely applied in oncology, immune-mediated diseases, endocrinology, and dermatology, with evidence supporting safe switching in stable patients. Market adoption faces challenges such as patent barriers, provider/patient hesitancy, contracting practices, and manufacturing scale-up, which can be mitigated by education, regulatory clarity, and quality-by-design approaches.

Clinical and methodological developments focus on switching strategies, immunogenicity monitoring, adaptive trials, PK/PD evaluation, and patient-reported outcomes. Post-marketing pharmacovigilance emphasizes accurate traceability, real-time safety monitoring, and data integration across registries and EHRs to ensure ongoing safety and confidence in biosimilar use.

Conclusion

Biosimilars have progressed from cautious experimentation, to now being routinely deployed in many high-burden diseases. The scientific convergence on analytical similarity, along with real world evidence trending, demonstrates feasibility for broader use and responsible extrapolation. Future development will also be shaped by smarter development (AI/ML), robust covigilance, procurement reform, and patient-centered implementation in an effort to realize affordability without sacrificing safety or quality.

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Copyright

Copyright © 2025 Ms. Reshma Dhakate, Shravni Jambhulkar, Shyamal Jadhav, Sara Kawthankar, Sarvesh Patil, Shamit Waghmare, Arshad Tamboli. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.