Navigating the Biosimilar Landscape: A deep-dive into Regulations, Challenges & Future Trends in the EU and US
A Q&A with Erik Doevendans, Technical Head (NL) Principal Consultant at Scendea
Introduction
The first regulation and guidance for similar biological medicinal products (‘biosimilars’) was introduced by the European Union, as it was considered impossible to make exact copies of biopharmaceuticals.
With that, the concept of biosimilarity is more a regulatory appreciation than a scientific definition. Other regulatory regions soon followed with similar regulations and guidance based on the EU model and today there are about one hundred unique biosimilars on the market in the EU and US, of which about 70% are monoclonal antibodies, and we have just over 16 years and more than one million patient years of clinical experience since the approval of Omnitrope in 2007.
What would you consider to be the key biosimilars that are in the race for approval in the next few years?
Part of the biosimilar pipeline contains the early biosimilars, such as filgrastim and pegfilgrastim, as well as molecules such as adalimumab and bevacizumab.
However, the pipeline for tumor necrosis factor inhibitors’ biosimilar development is also active, with 9 Stelara biosimilars at various stages of development. Also, tocilizimab, omalizumab and natalizumab will be part of the next gulf of copy biopharmaceuticals. Furthermore, following Stelara, Simponi and Cimzia are next, and other interesting biosimilar development is ongoing in the ophthalmology space, for example ranibizumab.
What are the biggest challenges biosimilar developers face when trying to meet regulatory requirements in the EU and US?
From a regulatory perspective, the expectations for biosimilars are highly aligned between US FDA and the EU EMA. It all starts with reverse engineering and demonstrating similarity in physicochemical and biological terms, followed by demonstration of clinical similarity. However, in the EU, any biosimilar is automatically interchangeable with the originator product, and vice-versa, whereas US requires additional clinical evidence to qualify as interchangeable.
When looking at EU, US and UK, what, if any, are the main differences when it comes to regulatory review and approval of such products?
Again, there are not many differences between these regions. Nevertheless, it seems that the UK MHRA will be the first to head to biosimilar acceptance without the comparative confirmatory clinical phase 3 studies.
Is it possible that future biosimilars will be approved without clinical data?
Biosimilars without clinical data are unlikely to ever be possible. However, and importantly, the EU and UK already offer the possibility to waive comparative efficacy trials with a clinical endpoint, and in principle, would allow PK/PD studies to demonstrate clinical comparability if appropriately justified. Scientifically, PK /PD studies provide a higher sensitivity than comparative studies with clinical endpoints, and notably that is a regulatory requirement.
Why would a developer want to gain authorisation of a biosimilar for an orphan condition?
The field of orphan medicinal products is an interesting one, companies may certainly want to pursue development of biosimilars of orphan drugs, and there are no regulatory limitations.
However, the market situation for Orphan drugs is quite unique. Having had the luxury of a lengthy market protection, the license holders of originator orphan biologics also hold the market in a tight grip, usually by knowing many of the individual patients treated with their medicine, although lower pricing may obviously help to leverage introduction of a biosimilar.
Conclusion.
As the biosimilar space continues to evolve, developers face complex challenges and growing regulatory intricacies. At Scendea, we can help guide you through the pathway of biosimilar development, providing expert support in both product development and regulatory activities.
Get in touch to speak to an expert, today…