Shift in EMA's biosimilar policy prioritizing clinical effectiveness experiments
The European Medicines Agency (EMA) has announced a significant policy shift, which could potentially revolutionise the biologics industry. The EMA's draft reflection paper, open for stakeholder comments until 30 September 2025, clarifies how it will consider biosimilarity requirements without the need for clinical efficacy studies (CES) in certain cases.
Biologics, with their active substances derived from biological sources, are often large, complex molecules with an inherent small degree of heterogeneity. The EMA's existing overarching guideline on biosimilars envisaged that in certain circumstances, a confirmatory clinical trial may not be necessary in the biosimilarity data package. The new proposal, however, requires an assessment of a biosimilar's quality attributes (QAs), providing detailed information on structure and functional properties essential for demonstrating similarity between the biosimilar candidate and the reference medicinal product (RMP).
The prerequisites for biosimilars to demonstrate comparability with reference products without the need for CES include comprehensive knowledge regarding the molecule's mechanism of action, detailed characterisation of the structure and functionally relevant QAs, availability of functional assays, a pre-established similarity assessment protocol, and a validated manufacturing process and control strategy.
The EMA notes that significant changes to manufacturing processes of biological medicines like monoclonal antibodies have been approved by confirmation of structural and functional comparability without the need for new clinical data. Pharmacokinetic (PK) studies would still be required in healthy volunteers to show that the product is processed in the same way in the human body, and they would also be used to test immunogenicity under the revised policy.
The move by the EMA could have a more seismic change for the industry, potentially accelerating the development of biosimilar orphan medicines, improving access to and affordability of life-saving treatments for patients with rare conditions. The Medicines and Healthcare Regulatory Authority (MHRA) in the UK has already updated its guidance in 2021, allowing biosimilar manufacturers to rely more heavily on comparative analytical and functional data to meet regulatory requirements.
It's important to note that the EMA's reflection papers do not constitute regulatory guidance, but 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's Biosimilar Medicinal Products Working Party will take account of all comments received and prepare a finalised reflections paper, expected to come into operation three months after publication.
Developing biosimilars and taking them through the regulatory process is expensive. However, biosimilars provide competition to originator biologics, often spurring innovation in the market. A new analysis from the IQVIA Institute in the US has revealed a massive biosimilar void: 90% of biologic drugs losing patent exclusivity over the next 10 years have no biosimilar competition in the pipeline. The EMA's regulatory policy shift could help address this void, making life-saving treatments more accessible and affordable.
The EMA will make its draft paper on the conditions for the marketing authorization of biosimilars that do not need to conduct CES available to the public in September 2025. The EMA's reflection papers can be used to facilitate discussion or provide clarification, particularly in areas where scientific knowledge is fast evolving or experience is limited. This policy shift is a significant step towards making biosimilars a more viable and accessible option in the treatment of various diseases.
