Regulatory and Clinical Perspective on Biosimilars: a Comparison of the US and European Experiences

Research paper by Niyati Vakil, John Fanikos

Indexed on: 15 Jun '19Published on: 15 Jun '19Published in: Current Emergency and Hospital Medicine Reports


The purpose of the review is to explore the reasons for low penetration of biosimilars in the United States (US) and to compare and contrast the US and European experiences.A biosimilar is a biologic that is highly similar to and with no clinically meaningful differences from an existing Food and Drug Administration (FDA)-approved reference product, where the reference product is the biologic that was originally approved by the FDA. The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created an abbreviated approval pathway (351(k)) for biosimilars to encourage their development and created provisions for interchangeability. Since then, 19 biosimilars have been approved and 7 have been marketed via this pathway; however, the market penetration and utilization of biosimilars in the US has been low. For example, infliximab-dyyb (Inflectra®), while approved in 2016, has captured less than 5% of the US infliximab market share. The European Union (EU) established a biosimilar pathway in 2005 with their first biosimilar approved in 2006. The biosimilar approval pathway in the EU and US are similar in that their goal is to prove biosimilarity. De novo studies to establish safety and efficacy of the biosimilar are not needed. In contrast, as part of the approval in the EU, a transition study in which patients are switched from a reference to a biosimilar is required. Individual countries are left to decide interchangeability. From a clinical perspective, the main concerns regarding biosimilars have been about switching patients from reference to biosimilars especially in clinically stable patients, a bias towards associating more adverse effects with biosimilars, and the differentiation of biosimilars used for chronic versus short-term conditions with objective efficacy measures. Finally, the idea that a biosimilar’s approval can be based on extrapolation from other indications has also led to reluctance in using them. Such clinical conundrums were likely also faced in the EU; however, its economic milieu has helped to increase adoption over the last decade. These techniques include price competition by using all available biosimilars, price regulation by national authorities, and incentives for prescribers to use biosimilars. While recognizing differences in the payer system, some or all of these techniques may help increase adoption in the US where individualized contracting and significant rebates offered by the reference products’ manufacturers have made switching to the biosimilar financially unfavorable.A pathway for accelerated biosimilar approval was developed in the US in 2009. Nonetheless, biosimilar penetration to the market remains low compared to the EU due to unique issues in the US, including the rebates provided by manufacturer of the reference biologic. While being sensitive to differences in payer structure between the US and countries in EU, it is possible to adopt some of their techniques.