Biosimilar Regulatory Development in US and EU

Biosimilar dev in US and EU
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As per the 2015 IMS report, the global biologics market is projected to reach 28% of the global pharmaceuticals market by 2020 [1]. This would translate to the biologics market potentially worth USD 390 billion in 2020. As many of the biologics will face patent expiration in the next 5 years, the biosimilar market is forecasted at USD 20 billion by 2020 [1]. Driven by the use of biosimilar products, the potential savings to health systems in the five major European Union (EU) markets and the United States (US), could exceed EUR 50 billion in over the next five years and reach as much as EUR100 billion depending upon the magnitude of biosimilar price reduction over reference biologics [2].

2016 marked a full decade since the approval of the first biosimilar medicine in Europe. Sandoz’s human growth hormone (HGH) Omnitrope® (somatropin) was the first biosimilar approved by EMA in April 2006 [3]. EU has been a major contributor in establishing the foundation for the global development of biosimilar regulatory frameworks and guidelines. The US Food and Drug Administration (FDA) has lagged behind the EMA with approval of first biosimilar (Zarxio® – filgrastim, Sandoz) in 2015, five years after the Biologics Price Competition and Innovation Act (BPCI) was passed [4].

Figure 1: Regulatory milestones in biosimilars, US and EU. A work product of RAS LSS Consulting.

Sources: EMA,  FDA

Both US FDA and EU´s EMA require totality of evidence, meaning that there is no single pivotal study that demonstrates biosimilarity but a collective information set generated via a stepwise approach to develop a biosimilar product. The analytical similarity is assessed through extensive structural and functional characterization of the proposed biosimilar and the reference biologic. Expression system, manufacturing process, receptor binding, immunogenicity and stability are some of the important factors while considering analytical similarity. The animal toxicity data is not mandatory but may be useful in establishing safety of the proposed biosimilar product wherever relevant. For establishing biosimilarity, both FDA and EMA (European Medicines Agency) expect an adequate clinical PK/PD (pharmacokinetic/pharmacodynamic) study, at least one clinical study comparing immunogenicity of the reference biologic and the proposed biosimilar, and a comparative clinical study to demonstrate non-inferiority of the proposed biosimilar product.

For regulatory purposes, the ultimate goal of the comparability exercise is to exclude any relevant differences between the biosimilar and the reference biologic products. Therefore, studies should be sensitive enough with regard to design, conduct, endpoints and/or population to detect such differences [5,6]. The regulatory agencies also maintain that there is no “one size fits all” assessment, each biosimilar marketing application will be reviewed on a case by case basis due to the inherent differences in the manufacturing process, product characterization and/or clinical development.

Figure 2: The difference in regulatory approval pathway for new biologic and biosimilar development. Adapted from: Lynne et al [7].

The goals behind the safe and regulated introduction of biosimilars into the market include increasing access to much-needed biologic medicines and reducing healthcare costs. Several biosimilar developers are eyeing the Oncology biosimilar opportunity. In the next part of this five part series, we will analyze the ongoing clinical development of biosimilars in Oncology therapy area.

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Richa Agrawal
Richa Agrawal
Richa leads the biosimilar practice at RAS. Having followed the evolution of biosimilar industry in last five years, she has acquired relevant understanding of this space which she like to share in her posts.

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