EMA to consult on biosimilars regulatory requirements in 2025

Experts at Pinsent Masons said the move could be a “game-changer” and help address the so-called ‘biosimilars void’ – an expected shortfall in the number of biosimilars that will be ready to be sold to rival originator biologics when protections providing market exclusivity to originator products end. This, in turn, could improve patient access to medicines and lower healthcare system costs across Europe.

Biosimilars provide competition to originator biologics, often spurring innovation in the market from biologics and biosimilars manufacturers alike – such as new clinical indications for existing products or improved delivery mechanisms. However, developing biosimilars and taking them through the regulatory process is expensive and there are further hurdles to clear in successfully bringing biosimilars to market when originator biologics lose their market exclusivity.

Biologics contain active substances derived from biological sources, such as mammalian cells, and are often large, complex molecules with an inherent small degree of heterogeneity. This marks biosimilars out from small molecule generic medicines, where the active ingredient is chemically identical to the originator drug. Nevertheless, biosimilars are highly similar alternatives to the originator reference product.

Currently, the EMA requires comprehensive scientific comparative efficacy studies to be carried out by biosimilar manufacturers to evidence ‘biosimilarity’ between their product and the originator biologic their product is based on, so as to obtain a marketing authorisation of their own. This entails conducting expensive and time-consuming clinical trials with patients.

While other medicines regulators globally, including the US Food and Drugs Administration, also require comparative efficacy trials to be carried out, the EMA is out-of-step with the UK’s Medicines and Healthcare Regulatory Authority (MHRA). According to guidance the MHRA revised in 2021, a comparative efficacy trial may not be necessary in most cases if sound scientific rationale supports this approach. That move allows biosimilar manufacturers to rely more heavily on comparative analytical and functional data as well as what is known from clinical experience and quality attributes of the originator biologics product, to meet their regulatory requirements.

The EMA’s approach is currently under internal review. In November last year, it published a concept paper in which it consulted on a tailored clinical approach in biosimilar development and confirmed some changes to regulatory requirements around clinical efficacy trials were under consideration.

The EMA’s consultation closed on 30 April 2024. Out-Law recently asked the EMA to confirm when it is expecting to set out its next steps.

In response, the EMA confirmed that it is in the process of drafting a “reflection paper” – one of many different types of documents that the EMA publishes – and plans to consult on it sometime in 2025.

While concept papers are “primarily intended to convey the need for discussing specific issues, innovations or controversial key-points at any stage of the development of medicinal products with a view to laying down the foundation for future guidelines”, they are typically short documents that do not explore potential solutions in detail.

The EMA said it will publish a reflection paper as a follow up to its earlier concept paper. Reflection papers can be used to facilitate discussion or provide clarification, “particularly in areas where scientific knowledge is fast evolving or experience is limited”, and, while the information in them does not constitute regulatory guidance, they can be a vehicle for the EMA to “communicate the current status of discussions or to invite comment on a selected area of medicinal product development or a specific topic”.

The EMA said “the exact timing” of the public consultation on its reflection paper “will depend on the availability of the mature draft”.

Amsterdam-based Carly van der Beek of Pinsent Masons said: “Since the early 2000s, many biological medicinal products have entered the market. Between then and now, a wealth of information on biologicals such as mAbs has become available. The EMA, adjusting to this reality, recognises that similarities at the analytical and functional level have increased the comparability for biosimilars while maintaining the highest standards of safety and efficacy.”

“This can be a game-changer, increasing the options for patients and prescribers navigating the market. Moreover, as the drug-budget can be used more efficiently, this may allow for the use of newer, high-cost treatments,” she added.

London-based Tracey Roberts of Pinsent Masons said: “If the reflection paper indicates comparative efficacy trials are not needed by the EMA, and other functional and clinical data will suffice, this could have a significant market impact. It would reduce costs of entry for biosimilars in Europe and enable manufacturers to consider to developing products where a business case may previously have been untenable. Biosimilar companies should look to the reflection paper with interest and participate in the consultation in 2025. They will want certainty from the EMA on the requirement, or lack thereof, for comparative efficacy trials, so they can plan accordingly.”