Ten years of biosimilars in Europe: development and evolution of the regulatory pathways

Abstract

A biosimilar is defined by the European Medicines Agency as a biological medicine that is similar to another biological medicine that has already been authorized for use. A science-based regulatory framework to ensure high-quality biosimilars has been established in Europe since 2005 and is monitored and updated on an ongoing basis. The guiding principle of a biosimilar development program is to establish similarity between the biosimilar and the reference medicine by the best possible means, ensuring that the previously proven safety and efficacy of the reference medicinal product also applies to the biosimilar. Development of a biosimilar is underpinned by state-of-the-art analytical techniques to characterize both reference medicines and biosimilars. The extent and nature of the nonclinical in vivo studies and clinical studies to be performed depend on the level of evidence obtained in the previous step(s), including the robustness of the physicochemical, biological, and nonclinical in vitro data. Extrapolation is an important element of the biosimilarity concept. When biosimilar comparability has been demonstrated in one indication, extrapolation of the data package to other indications of the reference medicine could be acceptable, but needs to be scientifically justified and considered in light of the demonstrated level of sameness by all analytical, nonclinical, and clinical data. The credibility of the scientific basis behind the biosimilar concept, and quality of regulatory decision-making, is demonstrated by the successful approval and clinical use of 20 biosimilar medicines since 2006 when Omnitrope® was the first biosimilar to be approved. The regulatory environment for biosimilars continues to evolve, both in recognition of advances in technology/analytical methods and the availability of new targets for biosimilar development.

Barriers towards effective pharmacovigilance systems of biosimilars in rheumatology: A Latin American survey

“…The European Medicines Agency (EMA) guidelines for approval of biosimilars are well established; the first biosimilar was approved in the European Union (EU) in 2006 . However, guidance regarding interchangeability, switching, and substitution of a reference product with a biosimilar is determined by individual EU member states .…”

Biosimilars: considerations for clinical practice

“…Patients and clinicians need to understand the potential cost and clinical implications of switching to biosimilars, but almost a decade of experience in clinical practice has thus far raised few concerns 46. Data from clinical trials and real world observational studies that specifically examine switching continue to accrue, providing a growing evidence base to aid clinical decision making.…”

Quality, Non-clinical and Clinical Considerations for Biosimilar Monoclonal Antibody Development: EU, WHO, USA, Canada, and BRICS-TM Regulatory Guidelines

“…In this review, we present quality, non-clinical and clinical requirements for the development of biosimilar mAbs and for their licensing by the EMA (overview of EMA guidelines related to the development and approval of biosimilars) (Schiestl et al, 2017), the WHO, USFDA, BGTD/HC, ANVISA/Brazil, Russian Federation/Russia, CDSCO/India, CFDA/China, SAHPRA/South Africa, TMMDA/Turkey, COFEPRIS/ Mexico. We have referenced and interpreted general biosimilar guidelines where guidelines specific to mAbs are unavailable.…”