EU proposes tailored approach to streamline biosimilar development

The European Medicines Agency (EMA) initiated a public consultation at the start of April on a draft reflection paper proposing a tailored clinical approach to biosimilar development. The paper suggests moving away from the traditional requirement for comparative clinical efficacy data, advocating instead for a scientifically robust model where bio-similarity can be demonstrated through comprehensive analytical and pharmacokinetic (PK) evidence alone.

The consultation is open for stakeholder comments until 30 September via the EU survey platform. If adopted, this tailored approach could streamline regulatory expectations, reduce development costs and increase the availability of biosimilars for EU patients.

Centralised regulatory submissions

The reflection paper is the result of years of regulatory experience and scientific advancements in biosimilar development within the EU. It builds on an EMA 2024 concept paper, which explored the feasibility of replacing confirmatory efficacy trials with a more risk-proportionate data package.

If implemented, the reflection paper’s proposals would impact the structure and expectations of marketing authorisation applications (MAAs) for biosimilars.

Historically, biosimilar MAAs submitted via the centralised procedure have included quality comparability data, non-clinical evidence, comparative PK studies, and at least one comparative clinical efficacy trial – unless a validated pharmacodynamic (PD) surrogate endpoint was available.

Under the proposed tailored approach, the requirement for a confirmatory clinical efficacy study could be waived if high similarity is demonstrated in physicochemical properties, biological activity and PKs.

Applicants may need to submit an enhanced analytical and statistical dossier, shifting investment from clinical to laboratory-based development. This could reduce overall costs and development time, while placing greater emphasis on precision analytics, statistical justification and manufacturing consistency.

Clinical and non-clinical studies

The reflection paper emphasises the analytical and quality foundations of the tailored approach. It asserts that the clinical effect of a protein-based medicine is determined by its molecular structure. Therefore, if a biosimilar is structurally and functionally indistinguishable from its reference product, their efficacy and safety profiles should be equivalent.

The paper outlines prerequisites for the quality comparability package, encouraging advanced statistical methodologies to evaluate similarity conditions and acceptance criteria for each quality attribute.

Under the proposed model, biosimilar clinical development may be limited to a single comparative PK study, with confirmatory efficacy trials waived in suitable cases. This marks a shift from current expectations, where a phase III comparative study is often required unless a validated PD surrogate endpoint is available.

The EMA justifies this potential change by noting that confirmatory efficacy trials have historically added little value when analytical and PK comparability are established. Such trials may also be infeasible for products with limited patient populations or narrow therapeutic indications.

The EMA has concluded that waiving a clinical efficacy study is acceptable only when the quality data package provides “solid evidence for similarity”. This information can be inferred from the totality of analytical, in vitro, and PK data. However, a comparative PK study in humans remains essential.

Where the mechanism of action is not well understood, or sensitive analytical methods are lacking, a comparative efficacy trial remains necessary.

EU pharma package

The reflection paper aligns with the broader EU pharmaceutical strategy and proposed reforms under the EU's "pharma package", currently being negotiated at European Council level. The legislative proposals published by the European Commission in April 2023 aim to modernise pharmaceutical legislation, reduce regulatory burdens, and support timely access to medicines. A key theme is promoting competition and the uptake of generics and biosimilars.

The EMA’s tailored approach contributes directly to this objective by reducing the complexity and cost of biosimilar development, encouraging market entry, and improving availability. This is crucial as Europe anticipates a new wave of biologic patent expiries in areas such as oncology and rare diseases.

While the reflection paper is not a legislative initiative, its adoption would reinforce the goals of the pharma package by facilitating earlier access, reducing unnecessary trial duplication, and preserving healthcare resources.

Osborne Clarke comment

The proposed tailored approach set out in the EMA's draft reflection paper would, if adopted, reduce reliance on clinical efficacy trials, shorten development timelines and improve the economic viability of biosimilar launches, especially for complex or niche biological products.

For pharmaceutical companies and biotech developers, high-quality analytical and PK data will become even more critical. Investment in orthogonal characterisation techniques, validated bioassays and statistical modelling will be essential. Early engagement with the EMA is strongly advised to validate the chosen development strategy.

While the paper focuses on the EU context, it also has implications for companies outside the EU. Developers targeting global markets may find that an EMA-compliant data package under the tailored approach aligns well with requirements of other regulators, such as the UK Medicines and Healthcare products Regulatory Agency and the World Health Organization. However, companies will also be monitoring the US Food and Drug Administration’s position, which may retain different expectations for certain product classes.

Companies have until 30 September to submit comments to the public consultation. They may also want to review their development programmes to assess the applicability of a tailored approach.