Fast-track trial approval: a way to jump the EU queue?

For early-stage biotechs, the transition from preclinical development to their first-in-human (FIH) clinical trial is one of the most high-stakes milestones in the company’s lifecycle and a defining metric for investment. Navigating the optimal regulatory route is a vital part of this journey. Choose wisely, and you can go from Phase 1 Clinical Trial Authorisation (CTA) application to approval in just a few weeks. Get it wrong, and you risk running into frustrating and costly delays at a time when every month of runway matters. 

With a population of roughly 450 million, representing about a quarter of global pharmaceutical sales, the EU is a key market for early phase clinical trials and subsequent approval. However, the multinational makeup of the bloc has historically posed a significant regulatory challenge, with separate CTA applications required for the National Competent Authority (NCA) in each country where a trial would be run.

The EU centralisation paradox

The EU Clinical Trials Regulation, enacted in early 2022, aimed to streamline the process by providing a single point of entry: the Clinical Trials Information System (CTIS). Under this model, a sponsor submits a single CTA through CTIS, selecting a Reporting Member State (RMS) to centralise the scientific assessment of the application, while each Member State Concerned (MSC) handles ethical review separately.

As the dust has settled on the first years of this centralised system, a new reality has emerged. While the process is simpler for sponsors, it has not necessarily become faster, as the internal coordination required between dozens of agencies has created a bottleneck. For standard drugs, such as small molecules or monoclonal antibodies, the typical approval timeline is approximately 76 days if no questions are raised by any regulatory authority. When requests for further information are triggered, the clock stops and the timeline extends, often significantly if new data needs to be generated. In practice, we’ve seen approval timelines for multinational trials are often stretching from the typical 90 days under the old system to closer to 110 days. 

Recognising that these lengthy timelines could discourage early-phase innovation and investment – particularly when compared with the US FDA’s 30-day approval process – individual European nations and the EU collectively are launching new accelerated pathways. For a biotech racing from funding to first patient dosed, understanding these shifts is a core strategic necessity.

New fast tracks

A number of EU members states have implemented fast-track assessment routes for trials conducted only within their borders, known as mononational trials, which can slash the time taken for Phase 1 approval.

For example, France has launched a national fast-track pathway specifically targeting trials of innovative therapies for serious or rare diseases with no existing treatment or first-in-class therapies with novel mechanisms of action. For a clean dossier with no questions, the French fast-track aims for authorisation in just 14 days. Even with questions, the maximum timeline is capped at 49 days, which represents a significant improvement over the standard centralised route.

Similarly, Belgium’s Federal Agency for Medicines and Health Products is committed to assessing mononational Phase 1 and Phase 1/2 trial applications within a maximum of 20 days. The country is also pioneering a multinational pilot phase for applications where it is the Reporting Member State, aiming for a 35-day assessment window. Other countries, including Spain and Germany, are also bringing in similar fast-track routes designed to attract innovation and speed up timelines.

Parallel to these national efforts is the Facilitating and Accelerating Strategic Clinical Trials (FAST-EU) initiative – a voluntary pilot coordinated by the European Heads of Medicines Agencies (HMA) network and the Clinical Trials Coordination Group (CTCG). FAST-EU targets multinational trials involving more than one Member State and aims for an overall duration of 70 calendar days from CTA submission to a final decision, including the time the sponsor spends responding to questions. This is an ambitious internal coordination target that operates within the CTR’s existing legal framework but uses parallel workflows to shave weeks off the process.

However, participation in FAST-EU is not automatic, and it is currently limited to a small number of applications, with a target of two trials per month. Selection criteria favour trials with a high number of participating Member States and those that have already engaged in EU-level pre-assessment activities, such as EMA Scientific Advice or the priority medicines (PRIME) scheme, which accelerates the clinical development of treatments for unmet medical needs.

Finding the fastest route

When the clock is ticking from closing a successful funding round to dosing the first patient, choosing where to run Phase 1 is a critical decision.

For Phase 1 studies outside of oncology, participants are usually healthy volunteers. Since most European nations have the clinical infrastructure to conduct these studies safely and effectively, having access to investigators specialising in your ultimate disease indication is less of a factor than it will be when you get to Phase 2. This gives biotechs the flexibility to prioritise speed of authorisation over geographical location.

For example, a company might choose to run a mononational Phase 1 trial in a country with fast-track approval, then add additional Member States later for Phase 2. Alternatively, if a trial requires a broad, multinational patient population from the start, applying for a FAST-EU pilot slot becomes the strategic priority.

The fastest route to first-in-human also depends heavily on the product’s nature. Standard medicinal products such as small molecules and monoclonal antibodies typically enjoy the smoothest path through these accelerated routes.

However, advanced therapy medicinal products (ATMPs), such as cell and gene therapies, often face additional scrutiny.

In the examples mentioned previously, ATMPs and certain biological products going through the Belgian accelerated approval process are subject to a 10-day extension. By contrast, the fast-track process in France specifically notes that for innovative therapies and ATMPs there is no additional delay, compared with up to 50 days of additional evaluation under the standard EU timeline.

While going from clinical trial application to approval in the EU in under a month is now possible, the margin for error has narrowed significantly. In this fast-paced regulatory environment, a carefully-compiled and thorough CTA is essential. Biotechs must ensure their Investigational Medicinal Product Dossier (IMPD), nonclinical data and clinical trial protocols are scientifically sound and meticulously aligned with the specific nuances of the chosen Reporting Member State and fast-track pathway.

What’s clear is that the clinical trials landscape in Europe is undergoing its most significant regulatory transformation in decades. Designed to reduce administrative burden, the unintended consequence of regulatory harmonisation is the emergence of further complexity as member states position themselves as premier destinations for innovative fast-track trials. 

Plotting a course to the clinic now involves navigating the interplay between the centralised Clinical Trial Authorisations, national fast-tracks and EU pilots. For biotech leaders, the challenge lies in making the right choices at the outset, seeking appropriate expert advice and support to put together the strategy and documentation that will enable innovative medicines to get into the clinic as efficiently as possible. ν

Jonathan Kearsey

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About the author: Jonathan Kearsey, PhD is a ­biopharmaceutical executive with nearly thirty years’ experience in early-stage drug development, regulatory affairs and biotech strategy. He is co-founder and Managing ­Director of Leads To Development, a consultancy that helps innovative biotechs advance their drugs to and through clinical trials as efficiently as possible. Previously, he held ­several director positions in French and Belgian biotechs where he was responsible for drug development activities and intellectual property portfolios.

This article was originally published in EBM’s summer edition. Get it here.